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Triggers for the onset and recurrence of psoriasis: a review and update
Cell Communication and Signaling volume 22, Article number: 108 (2024)
Abstract
Psoriasis is an immune-mediated inflammatory skin disease, involving a complex interplay between genetic and environmental factors. Previous studies have demonstrated that genetic factors play a major role in the pathogenesis of psoriasis. However, non-genetic factors are also necessary to trigger the onset and recurrence of psoriasis in genetically predisposed individuals, which include infections, microbiota dysbiosis of the skin and gut, dysregulated lipid metabolism, dysregulated sex hormones, and mental illness. Psoriasis can also be induced by other environmental triggers, such as skin trauma, unhealthy lifestyles, and medications. Understanding how these triggers play a role in the onset and recurrence of psoriasis provides insights into psoriasis pathogenesis, as well as better clinical administration. In this review, we summarize the triggers for the onset and recurrence of psoriasis and update the current evidence on the underlying mechanism of how these factors elicit the disease.
Video Abstract
Background
Psoriasis is a T-cell-mediated chronic inflammatory skin disease, which is characterized by excessive proliferation of keratinocytes (KCs) as well as redness caused by dilated dermal blood vessels and infiltration of immune cells [1]. Immune-related cells including dendritic cells (DCs) and T helper (Th) 17 cells, along with Toll-like receptors(TLRs) and cytokines such as interferon (IFN)-α, tumor necrosis factor (TNF)-α, IFN-γ, Interleukin(IL)-12, IL-22, IL-23, and IL-17, are responsible for the pathogenesis of psoriasis [2]. However, the exact etiology and pathogenesis are awaited to be elucidated [3]. Genome-wide association studies (GWAS) have identified more than 60 psoriasis susceptibility loci, which largely contribute to a better understanding of disease mechanisms and related pathways [1]. Still, it appears that the loss of immunological tolerance is a result of the close interplay between genetic factors and environmental triggers [4]. Therefore, identifying these specific triggers and unraveling their mechanism are crucial for the development of new therapies or interventions for psoriasis. This review is focused on the triggers for psoriasis, including extrinsic and intrinsic risk factors. The former include infections [5], skin trauma [6], lifestyles [7,8,9], mediation [10,11,12,13,14,15], humidity [16], cold weather [16], and air pollution [17]; while the latter include microbiota dysbiosis [18, 19], stress [20], dysregulated lipid metabolism [21], and dysregulated sex hormones [22] (Fig. 1).
It is worth noting that these risk factors have the potential to trigger both the onset and the recurrence of psoriasis, especially when these triggers persist as long-term stress events. Beyond the relevant triggers that will be discussed in this review, the underlying mechanisms of psoriasis recurrence at the originally affected sites are intricately linked to tissue-resident memory cells (TRM) in the skin [23]. In psoriatic plaques that have resolved after treatment, CD8 + TRM are retained within the epidermis, while CD4 + TRM the dermis. They all derived from their respective circulating memory cells [24]. When stimulated by triggering events, DCs and Langerhans cells secrete IL-23, which interacts with IL-23R on the surface of TRM, particularly IL-17‒producing CD49a–CD103 + CD8 + TRM, resulting in the reinitiating of inflammatory loops in the psoriatic skin [25]. Furthermore, the concept of a "molecular scar" within the epidermis of resolved lesions has been proposed, which is characterized by the inability of a specific set of genes, including those coding proinflammatory molecules IL-12, IFN-induced guanosine triphosphate binding protein Mx1 (MX1), IL-22, IL-17 and IFN‐γ, to revert to their normal expression levels [26].
Infections
The theory that psoriasis is infection-provoked has been widely concerned. Various microorganisms have been reported as the triggers of psoriasis, and many efforts have been devoted to the clarification of the mechanisms (Fig. 2). The pathogens that provoke psoriasis are summarized in Table 1.
Streptococcus pyogenes
It has been acknowledged that tonsillar infections caused by S. pyogenes can trigger or exacerbate psoriatic skin lesions in both plaque and guttate psoriasis [27, 50]. Researchers have linked streptococcal throat infections to psoriasis through genetic association studies, suggesting the recognized psoriasis risk allele HLA-C*06:02 as a risk factor for streptococcal tonsillitis and the imputed psoriasis risk haplotype HLA-C*06:02/HLA-B*57:01 as the strongest risk for tonsillitis [51, 52]. A clinical cohort study also reported that pediatric psoriasis aging from 10 to 11 was strongly associated with recurrent tonsillitis [53]. The same T cell clones were observed in psoriatic patients’ skin and tonsillar tissue, proposing the production of pathogenic T cells within the tonsils in post-streptococcal disorders [54]. Accordingly, tonsillectomy has been recommended as an intervention to resolve psoriasis, which can decrease the number of circulating T cells [55, 56]. Still, long-term follow-up should be conducted to verify the indication and long-lasting benefit of tonsillectomy [57]. Meanwhile, there is no solid evidence of the effectiveness of anti-streptococcal interventions [58]. Interestingly, the perianal streptococcal infection can trigger guttate psoriasis as well, but it appears less common than throat infections [59].
A classical explanation for the pathogenetic links between S. pyogenes throat infections and psoriasis is molecular mimicry. CD8 + T cells recognize epitopes shared by streptococcal M proteins and human keratin 17 (K17) in psoriatic patients, and K17 can become the self-antigen and target of the CD8 + T cells infiltrating the psoriatic skin lesions in an HLA-C*06:02–restricted pattern [60, 61].
The interaction of skin-seeking cutaneous lymphocyte-associated T cells (CLA + T cells) with S. pyogenes provides novel concepts to understand the immunopathogenesis of psoriasis [62]. Through stimulation of the IL-12 production pathway, S. pyogenes superantigens induce the expression of skin-specific homing receptors (the CLA antigen) on T cells and promote the migration of CLA + T cells to the skin [63]. Moreover, a high Th17 response has been observed in the cultures of CLA + T cells and epidermal cells from HLA-C*06:02–associated psoriatic patients with streptococcal tonsillitis [64]. S. pyogenes can induce IL-17 production in circulating CLA + T cells both in plaque and guttate psoriasis, which further induces psoriasis autoantigens (such as ADAMTS-like protein 5 and LL-37) after the CLA + T cells migrate to the skin [65]. In a psoriatic model in vitro, extracts of S. pyogenes induced the CLA + T cells to produce IL-9, which upregulates IL-17A production [66].
S. pyogenes peptidoglycan (PG) is also responsible for T cell activation in psoriasis. PG-containing macrophages are in close contact with PG-specific CD4 + T cells in psoriatic lesions, then the PG-specific CD4 + T cells proliferate and produce IFN-γ in an HLA-DR allele-restricted manner [67]. Additionally, the altered innate recognition of PG enhances the responses of T cells to S. pyogenes and induces psoriasis [68].
Staphylococcus aureus
S. aureus colonizes psoriatic skin lesions and nares in approximately 60% of psoriasis patients, while the colonization is observed in 5% to 30% of healthy individuals [10]. S. aureus was isolated from the throats of 11 of 22 psoriasis patients [69]. A study revealed an increase in inflammatory skin response to superantigen toxins in psoriatic subjects and an increased level of TNF-α mRNA in the psoriatic epidermis compared to healthy controls. However, the selective expansion of T cells expressing specific T cell receptor Vβ, a hallmark of superantigen stimulation, was not seen in psoriatic lesions. This T-cell-independent response might be explained by the higher expression of HLA-DR in KCs that enhanced inflammatory skin responses to superantigens [70]. Additionally, the severity of psoriasis was shown to significantly correlate with the production of staphylococcal enterotoxin, though mechanisms underlying this phenomenon remain unclear [71].
Commensal bacteria of the oral cavity
During periodontitis, the oral microbiota may affect the development and exacerbation of psoriasis [72]. A meta-analysis involving 13 studies has shown that the risk of developing psoriasis was higher in patients with periodontitis than in the control group [73]. One patient with initial guttate and later plaque psoriasis was cutaneously infected with Mycoplasma faucium, an oral Tenericutes species, which presented in the KCs of psoriatic stratum spinosum and extracellularly in the upper dermis of the psoriatic lesions [29]. Higher varieties and concentrations of oral bacterial (Porphyromonas gingivalis and Prevotella nigrescens) DNAs were also found in serum and synovial fluid of psoriatic arthritis (PsA) patients compared to controls (osteoarthritis) [30].
P. gingivalis and Aggregatibacter actinomycetemcomitans, pathogens associated with perodontitis, can activate human CD14 + monocytes to enhance Th17 differentiation and IL-17 production in vitro. P. gingivalis proteases can enhance Th17 lineage responses by degrading other crucial cytokines like IL-12, and myeloid antigen-presenting cells (APCs) are triggered to produce Th17-related cytokines IL-1β, IL-6, and IL-23 [74]. However, compared to healthy subjects, the frequency of IL-17 + cells was increased in patients with periodontitis in gingival tissue, not in peripheral blood [31].
Viruses
The skin inflammation in psoriasis can be triggered by the viral infection through the dysregulation of the antiviral immune response of hosts. Retinoic acid inducible-gene I (RIG-I) is the main cytoplasmic sensor of viruses. By activating RIG-I antiviral signaling, the infection of viruses can trigger the expression of IL-23 in the CD11c + DCs in genetically predisposed individuals, thereby leading to the development of psoriasis [75].
Human Immunodeficiency Virus (HIV)-infected patients have higher standardized incidence rates for psoriasis as compared to the general population [76]. HIV can directly trigger psoriasis as a source of superantigens or as a costimulatory factor in antigen presentation [34], and more IFN-γ is produced by activated CD8 + T cells during HIV infections [77]. The neuropeptide substance P can be released from HIV-infected immune cells and then modulates inflammatory and immune responses and stimulates the proliferation of KCs [78]. Human papillomavirus (HPV) is noted to be associated with psoriasis as well. A nationwide population-based cohort study that enrolled 66,274 patients with HPV infections revealed a higher prevalence of psoriasis after HPV infections [35].
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) was also proposed to be responsible for the exacerbation of psoriasis [5]. An enhanced level of inflammatory cytokines was observed in the plasma of SARS-CoV2-infected patients, and the concentrations of granulocyte-colony stimulating factor and TNF-α were associated with disease severity [79]. Additionally, some patients who received COVID-19 vaccines were reported to suffer from the exacerbation of chronic immune-mediated dermatoses like psoriasis, but the cutaneous reactions were generally mild and self-limiting [80, 81].
Nucleotide-binding domain and leucine-rich repeat pyrin domain-containing protein 1 (NLRP1) was one of the identified inflammasome-forming pattern recognition receptors (PRRs), by which the innate immune system can detect pathogens. Long double-stranded RNA (dsRNA) generated in the course of infections of positive-strand RNA viruses, e.g., Semliki Forest virus, can bind and activate NLRP1 inflammasome in human keratinocytes [82]. NLPR1 inflammasome has been implied in prompting the onset of psoriasis, either by increasing the susceptibility to psoriasis or by dysregulated release of pro-inflammatory cytokines including IL-1β and IL-18 [83,84,85]. Very similarly, NLRP1 has the capacity to sense bacterial pathogen exotoxin, such as exotoxin A secreted by Pseudomonas aeruginosa and diphtheria toxin by Corynebacterium diphtheriae, and induce cell death and IL-1β/ IL-18 secretion [86].
Other pathogens: fungal microbiota, helicobacter pylori, and so on
Diverse fungi in psoriatic skin have been identified to activate psoriasis through the innate immune system in genetically predisposed individuals [87]. As a typical example, Candida albicans has been frequently found in intertriginous psoriasis. Superantigens derived from microbes such as C. albicans might lead to the exacerbation of psoriasis in infected patients [88]. Exposure to C. albicans can also trigger a clinically relevant response to IL-17 in psoriatic skin [47]. Psoriatic CLA + T cells/ epidermal cells co-cultures responded to C. albicans extract by increasing the production of IL-9, IL-17A, and IFN-γ [66]. Moreover, cutaneous C. albicans infection induced recurrent psoriasis through IL-17-producing CD4 + TRM. In a mouse model, the CD4 + TRM become the main source of IL-17 after 30 days of infection. Other than C. albicans, Malassezia organisms may be implicated in the exacerbation of scalp psoriasis [49].
Compared to the control groups, H. pylori infections were significantly increased among moderate and severe psoriatic patients, but not among mild psoriatic patients [32]. In psoriasis patients with H. pylori infections, the Psoriasis Area and Severity Index (PASI) scores were higher [32, 89], so were the mucosal levels of psoriasis-associated cytokines IL-1β, IL-6, IL-8, and TNF-α [90]. However, a finding in 2015 argued that there was no increased prevalence of H. pylori in psoriasis individuals than in healthy controls [91].
Dysbiosis of skin and gut microbiota
Currently, much research has been devoted to the role of the human microbiome in the pathogenesis of psoriasis, especially the relationship between cutaneous and intestinal microbiomes, known as the “gut-skin axis” [18].
Several researchers have speculated that psoriasis may be closely associated with the dysbiosis of skin microbiota in the host (Fig. 2). A higher bacterial load but lower bacterial diversity in lesional psoriatic skin were recently revealed, compared to non-lesional skin and controls [92, 93]. Firmicutes and Actinobacteria are respectively the most common bacterial phylum in psoriatic patients and healthy controls [94], and an increased Firmicutes and a corresponding decrease in Actinobacteria were significant in lesional skin [95]. However, another study reported an increase in both Actinobacteria and Firmicutes in psoriasis lesions [96]. This discrepancy may be due to the variety of sampling methods, skin sites, medications, and analytical methodologies [97]. According to new evidence, compared to unaffected and healthy skin, psoriatic lesions have higher concentrations of Corynebacterium and lower concentrations of Cutibacterium [92]. Corynebacterium abundance was correlated with disease severity [92] and most species of Corynebacterium induce an intense IL-23-dependent response in mouse skin [98]. After smearing Corynebacterium pseudodiphtheriticum on mouse skin, the cutaneous IL-1β protein level and γδT17 cells in the dermis were increased [99]. Moreover, the psoriasis ear skin showed an overrepresentation of staphylococci [100]. A lower abundance of Staphylococcus epidermidis and Propionibacterium acnes may promote S. aureus colonization in psoriasis, which can stimulate Th17 polarization and trigger IL-17-mediated skin inflammation in a mice model [101].
A cycle from barrier destruction to microbiota disturbance, then to lesion aggravation was proposed to explain the pathogenesis of psoriasis [92, 102]. Mice with epidermal barrier defects have an increased bacterial load and antimicrobial peptides (AMPs) expression. The psoriasis-like phenotype in the mice could be relieved by reducing bacterial load on the skin after applying topical antibiotics, along with the decrease of IL-17 and IL-22 production [103].
Other than the dysbiosis of the skin microbiota, the disturbed gut microbiota also influences the pathophysiology of psoriasis [19, 104] (Fig. 3). The alteration of gut microbiota in both composition and functional potentials was confirmed in patients with psoriasis compared to healthy controls [105]. Psoriasis patients had significantly disturbed gut microbiota profiles, low bacterial diversities, and distinct relative abundances of several bacterial taxa [106]. The Firmicutes/Bacteroidetes (F/B) ratio is elevated in psoriasis and positively correlates with the PASI score. Besides Firmicutes and Bacteroidetes, 16 kinds of phylotypes at the genus level also significantly differ between psoriasis patients and healthy controls [107].
Intestinal fatty acid binding protein (FABP) is a biomarker of gut barrier integrity, and its level is positively related to the severity of psoriasis [108]. The gut microbiota dysbiosis may increase intestinal permeability, also called “leaky gut”, by reducing the thickness of the mucus layers, disturbing the proliferation and metabolism of intestinal epithelial cells, and affecting the production of AMPs [109]. Additionally, the gut bacteria may escape into blood by DCs through processes between epithelial cells without affecting tight junction function, or via microfold cells overlying Peyer's patches, presenting microbial products to APCs [110]. The leaky gut facilitates the translocation of bacteria and allows the entry of exterior antigens from the intestinal lumen to the blood and lymphatic circulations, driving both local and systemic immune responses [109]. Compared to other patients and healthy control groups, the increased bacterial DNA translocation in blood samples of those suffering from plaque psoriasis was caused mostly by intestinal bacteria, including Escherichia coli, Enterococcus faecalis, and Shigella fresneli. Patients with bacterial DNA translocation also showed higher levels of systemic inflammatory response [111]. Another study also reported that bacterial DNA was observed in the blood of 25% of patients with plaque psoriasis, and bacterial translocation was more likely to happen among patients grouped in enterotype 2 (predominance of Prevotella) compared to patients classified in other enterotypes [112]. These microbes may release highly potent inflammagens such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA) after being reactivated, which may contribute to the mild and chronic inflammation in the host organism, from which psoriasis patients suffer [113, 114]. Psoriasis can also be exacerbated by the bacterial endotoxins (ET) and PGs absorbed from the gut, which has been proven by the psoriasis treatment by preventing their absorption or breaking up endotoxins [115].
Moreover, the microbiota can modify immune activity through microbial metabolites in the gut. Short-chain fatty acids (SCFAs), as the major fermentation products of non-digestible carbohydrates by gut microbiome, mainly include acetate, butyrate, propionate [116]. Among them, butyrate was reported to enhance histone H3 acetylation at the promoter region of the Foxp3 locus, suggesting its potential to impact the differentiation of Treg cells [117]. Folate come from both gut microbiota and diet [118], and dietary folate has a selective effect on the maintenance of Foxp3 + Tregs [119]. As one of the host tryptophan metabolic pathways, the kynurenine routes can convert mature DCs into tolerogenic ones via indoleamine 2,3 dioxygenase, thereby enhancing Tregs and suppressing effector T cells [120]. These results may propose that microbiota metabolites act as non-infectious risk factors for psoriasis by triggering the differentiation of intestinal T cells.
Recently, much attention has focused on the function of group 3 innate lymphoid cells (ILC3s). ILC3s are primarily found in the intestine and skin [121] and are considered to play a pathogenic role in psoriasis by producing IL-17A and IL-22 [122]. When the body is infected with certain extracellular pathogens such as Citrobacter, ILC3s produce IL-22 and/or IL-17 for mucosal immunity against the pathogens [123]. The function of ILC3s can be also regulated by microbial metabolites such as SCFAs, including acetate, butyrate, and propionate. Butyrate can be produced by the Firmicutes, while acetate and propionate are mostly produced by the Bacteroidetes [124]. In mice, acetate and propionate bind to the SCFA receptor FFAR2 on colonic ILC3s, activate AKT or ERK signaling, and increase ILC3-derived IL-22 through an AKT and STAT3 axis [125]. However, microbiota-derived butyrate shows an opposite effect and decreases the amount of ILC3s in Peyer’s patches [126].
The treatment of probiotics has demonstrated potential benefits in the improvement of psoriasis, though no standardized treatment has been formulated [127, 128]. Fecal microbiota transplants offered another possible therapeutic strategy as they alleviate the autoimmune disease by allowing “eubiosis” from a healthy fecal microbiome to recolonize the gut of the affected patients [129]. In the future, a better understanding of microbiota dysbiosis would undoubtedly shed light on the treatments to alleviate psoriasis.
Dysregulated lipid metabolism
The association of obesity and dyslipidemia with psoriasis has been indicated by many studies [21, 130], but the molecular link between them is incompletely characterized. In general, adipose tissue may serve as an immune organ in patients with dysregulated lipid metabolism through hypertrophic adipocytes’ secretion of high amounts of hormones and cytokines (also called adipokines), including IL-6, TNF-α, and leptin, which modulate the inflammatory pathways and the activity of immune cells [131, 132]. Various psoriasis RNA-seq datasets have shown that lipid metabolism pathways are deeply involved in the pathogenesis of psoriasis [133]. Figure 4 illustrates the potential mechanisms linking dyslipidemia to psoriasis.
Recent studies have suggested that dietary components, independent of obesity-associated parameters, may play a critical role in the exacerbation of psoriasis [134,135,136,137]. A study using a mouse psoriasis model provided evidence that dietary free fatty acids (FFAs), especially saturated fatty acids (SFAs), are key amplifiers of psoriatic dermatitis. There are possible underlying mechanisms of SFAs-induced exacerbation of psoriatic dermatitis. Circulating SFAs are transported into the skin and induce the production of various proinflammatory cytokines from myeloid DCs, such as IL-1β. These proinflammatory cytokines subsequently facilitate the secretion of chemokines and inflammatory cytokines from KCs, which results in the recruitment of neutrophils and monocytes to the skin as well as the amplification of psoriatic dermatitis [134, 138]. SFAs could also modulate the NALP3 inflammasome in monocytes or macrophages and inflammasome-mediated IL-1β secretion through the activation of TLR2 and TLR4 [139, 140]. Another mechanism of SFAs in the exacerbation of psoriatic dermatitis is to promote Th1/Th17 differentiation via the activation of DCs [135, 141]. Additionally, the increase of FFAs in the body may be conducive to the recurrence of psoriasis by supporting the survival of TRM cells in the epidermis [142]. Moreover, components of dietary FFAs, middle- and long-chain fatty acids (MCFAs and LCFAs) direct the gut-shaped Th cell differentiation [143], which is opposite to the Treg differentiation by butyrate described above (Fig. 3).
Other than SFAs, polyunsaturated fatty acids (PUFAs) and PUFA-derived bioactive lipid mediators (LMs) were reported to mediate the inflammatory response in psoriasis. Among them, bioactive LMs derived from two PUFAs, linoleic acid (LA, n-6 PUFA) and α-linolenic acid (ALA, n-3 PUFA), which are respectively known for their pro- and anti-inflammatory properties in psoriasis [144]. As the representative n-6 PUFA-derived LMs, LTB4 contributes to neutrophil chemotaxis and PGE2 contributes to KC proliferation [144]. Specialized pro-resolving lipid mediators (SPMs) that derive from n-3 PUFA, including lipoxins (Lxs), resolvins (Rvs), protectins (PDs), and maresins (MaRs), have anti-inflammatory and immunomodulating functions in psoriasis [145, 146]. A research group focusses on the identification of bioactive LMs and SPMs in human psoriasis based on liquid chromatography-tandem mass spectrometry (LC–MS/MS) analyses. According to their studies, the bioactive LMs derived from n-6 PUFAs are abundant in psoriasis skin, while resolving D1 (RvD1), resolving D5 (RvD5), protectin D1 (PD1) and its double dioxygenation isomer 10S,17S-diHDHA (a.k.a. PDx), the aspirin-triggered forms of Lipoxin A4 and Lipoxin B4 (AT-LXA4 & AT-LXB4) may be the potent SPMs to resolve the inflammatory responses in the pathophysiology of psoriasis [147, 148].
Lipid metabolism is closely related to ferroptosis, and ferroptosis promotes cell death and triggers inflammation in psoriatic KCs, which involves a series of continuous events, i.e., the accumulation of reactive oxygen species (ROS) causes lipid peroxidation and further induces ferroptosis [149, 150]. During psoriasis, an enhancement of lipid peroxidation has been demonstrated by the positive correlation between lipid peroxidation and the Th22/Th17 pathway at a single-cell level [151]. KCs are also sensitive to ferroptosis in a time- and concentration-dependent manner [151]. In the lipid metabolism of KCs, accumulated PUFAs in circulation are catalyzed to the key substrate PUFA-CoA and finally esterified into PUFA-PLs, which can be peroxidized to PUFA-PL-OOH when there is bioactive iron. Subsequently, PLOOH can sensitize the cell to ferroptosis by generating lipid hydroxyl radicals and lipid peroxyl radicals. On the contrary, MUFA-CoA, the product of monounsaturated fatty acids (MUFAs) from SFAs, can reduce the available substrate for lipid peroxidation by inhibiting the peroxidization of PUFA-PLs, thus inhibiting ferroptosis. In addition, various studies have shown that Ferrostatin-1 (Fer-1), an effective inhibitor of lipid peroxidation, inhibits ferroptosis and blocks inflammatory responses in psoriasis [152].
Besides oxidative stress, lipids can also initiate endoplasmic reticulum (ER) stress, which has bidirectional effects: initial lipid-induced ER stress can be cytoprotective, but prolonged FFAs-induced ER stress might promote cell death [153]. In nonadipose cells, excess saturated FFAs induce both ROS and ER stress through lipid metabolism and signaling pathways. The following dysfunction of mitochondria and the ER are key steps leading to terminal cell death [154]. Moreover, prolonged ER stress can lead to oxidative stress and lipid-induced ROS may also trigger ER stress indirectly, though the precise mechanism is not clear yet [154].
The role of lipid autoantigen in driving dyslipidemia-related autoimmune diseases has also aroused attention [155]. Psoriatic lesions contain high levels of phospholipase A2 (PLA2), which involves in the production of neolipid skin antigens. Induced by IFN-α, the cytoplasmic PLA2 group IVD (PLA2G4D) can be released from psoriatic mast cells in the form of exosomes and transferred to neighboring CD1a-expressing Langerhans cells. Then neolipid antigens are recognized by the lipid-specific CD1a-reactive T cells, which release IL-22 and IL-17A [156]. Besides CD1a-restricted T cells, other CD1 molecules (such as CD1b and CD1c) -restricted T cells also respond to self-lipids and induce the production of cytokines. In a study, CD1b-autoreactive HJ1 T cells were directly activated by some autoantigens from accumulated phospholipids and cholesterol in skin lesions. In mice with hyperlipidemic serum, increased IL-6 production by CD1b + DCs and IL-17A secretion by HJ1 T cells were observed, indicating that the potential link between hyperlipidemia and psoriasis might lie in self-lipid-reactive T cells [157].
Psychological stress and other mental disorders
A systematic review demonstrated a possible correlation between psychological stress and the onset, severity, and recurrence of psoriasis [20]. Patients in 31–88% of cases reported stress as a trigger for psoriasis, and a higher incidence of psoriasis occurred in subjects bearing a stressful event in the previous 12 months [158]. Another case–control study, which utilized Holmes and Rahe’s Social Readjustment Rating Scale to evaluate stress life events, drew a conclusion that stress played a significant role in the development of psoriasis, particularly in terms of recurrences and extensions [159]. However, a meta-analysis reported there was no convincing evidence of this association between stressful events and psoriasis [160]. Thus, the relationship should be prospectively scrutinized in population-based studies in the future, utilizing standardized stress instruments, as well as incorporating additional physiological and biochemical stress markers [20].
Woźniak E et al. summarize that stress plays a role in the pathophysiology of psoriasis possibly through the hypothalamic–pituitary–adrenal (HPA) axis, immune pathways, and peripheral nervous system [161] (Fig. 5). In response to psychological stress, the hypothalamus produces corticotropin-releasing hormone (CRH), which further activates the secretion of the pituitary adrenocorticotrophic hormone (ACTH) and the adrenal cortisol. CRH is capable of suppressing the apoptosis of KCs, which is a typical phenomenon in psoriasis. On the other hand, CRH enhances angiogenesis by stimulating vascular endothelial growth factor (VEGF) and increases vascular permeability, facilitating the penetration of the inflammatory cells in the psoriasis plaques. Mast cells (MCs) can also be activated by CRH, and then release the cytokines and chemokines, including IL-1, IL-6, IL-31, TNF, and CXCL-8. Moreover, stress stimulates the release of neuropeptides from cutaneous peripheral nerve endings, leading to the development of neurogenic inflammation with the activation of MC. These neuropeptides include neurotensin (NT), substance P (SP), nerve growth factor (NGF), and the pituitary adenylate cyclase-activating polypeptide (PACAP) [161].
Apart from stress, the risk of developing psoriasis was significantly increased in patients with major depressive disorder or posttraumatic stress disorder than in the control group [162,163,164]. Even the association between parental common mental disorders (anxiety and depression) and offspring's risk of psoriasis has been determined [165]. Another study reported a woman with bipolar disorder subsequently developed psoriasis and experienced exacerbations in psoriatic lesions during each manic episode [166]. In accordance with the clinically elevated psoriatic inflammation in patients with autistic spectrum disorder, Nadeem et al. reported a high level of systemic inflammation in autistic mouse models, suggesting the link between autism and psoriasis activity [167]. Furthermore, previous research has established that a genetic overlap exists between severe mental disorders and psoriasis [168].
Dysregulated sex hormones
An increasing body of research has elucidated the diverse biological and immunomodulatory effects of sex hormones on the skin. The natural course of psoriasis appears to be modulated by pregnancy, menstruation, and menopause, thereby implying a plausible involvement of female hormone-induced mechanisms in modulating skin inflammation [169, 170]. Furthermore, studies have revealed a higher prevalence and severity of psoriasis in males compared to females, especially at the estrogen abundant age, indicating distinct regulatory effects of different sex hormones on psoriasis [171].
The current consensus suggests that estrogen exerts a protective influence on psoriasis. Estrogens have been found to potentially exhibit anti-psoriatic effects by downregulating IL-1β production from neutrophils and macrophages, a process mediated through estrogen receptors α and β (ERα and Erβ) [172]. Likewise, an in vivo study demonstrated that estradiol played a protective role in imiquimod (IMQ)-induced psoriatic inflammation in mice by modulating the functions of neutrophil and macrophage [173]. In-vitro 17β-estradiol blocked the positive feedback loop of IFN-γ/interferon-induced protein of 10 kDa (IP-10), which supports Th1-mediated inflammation in psoriasis [174]. Conversely, certain studies have proposed that estrogens may possess proinflammatory properties in psoriasis, aligning with clinical observations that symptoms of psoriasis improve in some pregnant patients while worsening in others [172]. A case report has indicated that a patient undergoing tamoxifen treatment, an antiestrogenic agent, obtained remission of psoriasis symptoms, but experienced worsening symptoms during the perimenstrual cycle [175]. It is noteworthy that male psoriasis patients exhibited substantial increases in serum estradiol level compared to controls, suggesting a potential involvement of estrogen in the development of psoriasis [176]. Furthermore, an in-vivo study using an imiquimod-induced psoriasis model also indicated that estrogen plays a pro-inflammatory role in psoriasis by inducing IL-23 through Erα [177]. Collectively, these pieces of evidence support the notion that estrogen may have dual effects on psoriasis in a context-dependent manner, which leads to occasional contradictory observations [172, 178].
Existing research indicates a protective role of progestogens in psoriasis, as evidenced by the clinical observation that psoriasis often improves or resolves during pregnancy but reappears after delivery [170]. A case–control study identified an correlation between the improvement in affected body surface area and an elevation in estradiol, estriol, and the estrogen to progesterone ratio among pregnant women [179]. Some researchers have demonstrated that KCs serve as targets of progesterone by expressing progesterone receptor (PR) in psoriatic skin [180]. Furthermore, progesterone induces transcriptional alterations during pregnancy, which are enriched with genes associated with psoriasis. STAT1 and STAT3 are significantly downregulated, and their downstream targets, including IL-12β, OSM, and CXCL10, are affected [22].
A few reports have explored the role of androgen deprivation therapy (ADT) in advanced prostate cancer (PCa) as a potential exacerbating or alleviating factor for psoriasis. A case report demonstrated psoriasis exacerbation in a PCa patient following ADT [181]. Conversely, an investigation found a correlation between ADT and a decreased risk of psoriasis [182]. A separate study revealed a significant inverse correlation between total testosterone or free testosterone and PASI, irrespective of age group [183].
In summary, current investigations exploring the influence of sex hormones on psoriasis primarily rely on observational studies with a dearth of in-depth mechanistic exploration. Those somehow contradictory findings on estrogen and androgen suggest the need for additional high-quality evidence to better comprehend the intricate association between sex hormones and the pathogenesis of psoriasis.
Other environmental triggers
The potential mechanisms responsible for triggers that cannot be classified into infectious factors, dysbiosis of skin microbiota, dysbiosis of gut microbiota or dysregulated lipid metabolism are illustrated in the Fig. 5.
Skin trauma or pressure
Skin trauma or pressure can trigger psoriasis, known as the Koebner phenomenon (KP) [6]. Cupping therapy, as traditional Chinese medicine, was used to heal psoriasis, but it is now controversial because some psoriasis patients develop localized skin lesions through KP instead of achieving desired therapeutic results. Cupping therapy leads to KP at the cupped sites in psoriasis patients [184, 185], and Hijama (a form of wet cupping performed in Middle East countries) results in KP only in the incision areas [186]. During skin injury, damaged KCs release self-nucleic acids, including dsRNA, single-stranded RNA (ssRNA) and DNA, and induce the expression of LL-37. LL-37 enables ssRNA or DNA recognition in plasmacytoid DCs (pDCs) by TLR7 or TLR9, which finally leads to the secretion of IFN-α [187,188,189]. LL-37 exposure can also induce the production of IFN-β, either through a DNA-LL-37 complex–independent mechanism or through the recognition of dsRNA by TLR3. For the former mechanism, LL-37 increase TLR9 expression, thereby promoting the recognition of TLR9 ligands, such as CpG or genomic DNA [190, 191]. IFN-α from pDCs along with IFN-β from KCs promote the maturation of conventional DCs (cDCs). The recurrence of psoriasis at trauma sites has been attributed to the accumulation and reactivation of TRM cells occurring at the sites [192].
A case report described that a woman developing psoriasis vulgaris complained of new psoriasis lesions after a tissue expander insertion. Mechanical stretch was suspected to trigger ATP (Adenosine 5'-triphosphate) release from KCs and subsequent production of Th17-polarizing cytokines, like pro-IL-1β and IL-6. The epidermal Langerhans cells could also be activated by the released ATP [193]. In a murine model of skin expansion, epidermal hyperproliferation, impaired skin barrier function, along with upregulation of psoriasis-associated cytokines in epidermal KCs were observed. In human KCs, a continuous stretching regime resulted in the production of psoriasis-associated proinflammatory cytokines, AMPs, and chemokines [194]. In addition to stretch, the scratch injury to KCs triggers the KP through cytokines or chemokines CCL20 and to a less extent CXCL8 in a scratch-line-number-dependent manner [195].
Lifestyles
The prevalence of ever smoking is higher in psoriatic patients compared with the general population [7], and the suggestive causal effect of smoking initiation and cessation on psoriasis was revealed [196]. Smoking intensity and duration may have a dose-dependent effect on the incidence of psoriasis [197, 198]. As an independent risk factor for the development of psoriasis, smoking has many negative effects on psoriasis patients, including a higher PASI score, elevated nail involvement, and the development of cardiovascular diseases [199].
Smoking may trigger psoriasis through inflammatory, oxidative, and genetic mechanisms. Nicotine stimulates innate immune cells, such as DCs, macrophages, and KCs, by releasing inflammatory cytokines. Besides, smoking initiates the formation of free radicals that activate protein signaling pathways involved in psoriasis. In the aspect of genetics, smoking upregulates the expression of psoriasis-associated genes, including HLA-C*06:02, HLA-DQA1*0201 and CYP1A1 [200]. A recent study has elucidated the involvement of CHRNA5, a nicotinic receptor gene, in the development and pathogenesis of psoriasis. Silencing CHRNA5 could inhibit the proliferation and migration of human KCs [201]. Interestingly, smoking also increases the risk of PsA in the general population, but smoking appeared a protective effect among psoriasis patients, which is known as “smoking paradox” [202]. However, a very recent Mendelian randomization study encompassing 105,912 individuals with full information on lifestyle factors, biochemistry, and genotype data suggests that smoking is an independent, but not a causal risk factor for psoriasis [203].
Sleep disorders have been commonly considered one of the risk factors for psoriasis. A nationally representative population-based dataset suggested that the risk of psoriasis and PsA increased when obstructive sleep apnea occurred [8]. Sleep loss may alter barrier homeostasis and the stratum corneum integrity through insomniac psychological stress [204]. Researchers revealed that pro-inflammatory cytokines (IL-1β, IL-6, and IL-12) were significantly increased and anti-inflammatory cytokines (e.g., IL-10) were decreased in mice with psoriasis after sleep deprivation. Sleep loss also promoted the activities of kallikrein-5 and kallikrein-7 in the psoriatic skin, which affected the epidermal barrier and led to the development of psoriasis [205]. Furthermore, cortisol increases in some sleep disorders like insomnia [206]. Cortisol stimulates skin MCs, disrupts skin barrier function, and upregulates pro-inflammatory cytokines, which further exacerbate psoriasis [207].
Dietary factors are being widely investigated for their role in psoriasis pathogenesis currently [9]. Some studies have addressed the potential role of gluten in psoriasis in several publications. Clinical improvements were seen in 73% of patients after adhering to a gluten-free diet for three months, and Ki67 lymphocytes were also reduced in the psoriatic dermis [208, 209]. Other than gluten, the increased sodium chloride (NaCl) intake is considered to have a potential effect on the pathogenesis of psoriasis (Fig. 3). Under high-salt conditions, activated p38/MAPK pathway can upregulate downstream targets nuclear factor of activated T cells 5 (NFAT5) and serum/glucocorticoid-regulated kinase 1 (SGK1). The upregulation of target genes can drive the expression of transcription factors RORγt, IL-23R, IL-17A, and IL-17F, which lead to the differentiation of psoriatic Th17 cells from naïve CD4 + T cells. SGK1 is critical for promoting IL-23R expression and stabilizing Th17 cell differentiation through the phosphorylation of Foxo1 [210, 211].
A complex and multifactorial relationship exists between psoriasis and alcohol consumption. Psoriatic patients have higher rates of excessive drinking than general people [212], and abuse of alcohol increases the severity of psoriasis and reduces treatment effectiveness [213]. There is also an increased risk of death in patients with moderate to severe psoriasis, and alcohol is a major contributing factor [214]. However, an investigation reported that alcohol consumption is not significantly linked to psoriasis development [215], and a Mendelian randomization study found no causal relationship between alcohol consumption and psoriasis as well [196]. There is still insufficient evidence to determine whether alcohol consumption implicates the onset and recurrence of psoriasis.
Medications
Numerous medications can trigger psoriasis, such as lithium, β-blockers, antimalarial agents, nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, IFN, IMQ, terbinafine, statins, fibrates, and anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) antibodies [10,11,12,13, 15]. In rare cases, TNF inhibitors may also paradoxically induce psoriasis [14].
Psoriasis is the most common cutaneous adverse effect of lithium [10]. The incidence of inducing and exacerbating psoriasis resulting from lithium ranges from 3.4 to 45% [216]. Lithium stimulates cell communication between psoriatic KCs and lymphocytes by inducing the release of IL-2, TGF-α, and IFN-γ [217]. Lithium also inhibits glycogen synthase kinase-3, a serine-threonine kinase, contributing to the activation of NFAT2 and the proliferation of human KCs [218]. Furthermore, lithium inhibits monophosphatase, an essential pathway for the recycling of inositol in intracellular signaling [219]. Lithium then interferes with intracellular calcium channels through the reduction of inositol, thus affecting the proliferation and differentiation of KCs [10].
When treated with β–blockers, CAMP-an intracellular messenger responsible for promoting cell differentiation and inhibiting proliferation-is shown to be decreased in the epidermis, finally leading to excessive proliferation of KCs [220]. In addition, important differences have been characterized in protein tyrosine phosphorylation activities between psoriatic T cells and controls, and the induction of protein tyrosine kinases is crucial in the activation and proliferation of cells including lymphocytes and KCs [221, 222].
Along with the rapidly growing use of anti-PD-1 or PD-L1 antibodies in the treatment of late-stage malignancies, cases of anti-PD-1/PD-L1-induced psoriasis have been gradually reported [223]. Exacerbation of existing psoriasis and newly onset psoriasis during the treatment have both been previously described [224]. Some researchers suggest that the inhibition of PD-1 promotes skin inflammation by accelerating the infiltration of epidermal CD8 + T cells, which are involved in pathogenic crosstalk with KCs. They further demonstrated the potential efficacy of IL-6–targeting therapy for anti-PD-1/PD-L1-induced psoriasis [225].
Other drugs are implicated in psoriasis through distinct mechanisms as well. For example, antimalarial drugs change the activities of enzymes, such as the modulation of transglutaminase activity, which is involved in the epidermal proliferation process [226]. IMQ, the innate TLR-7/8 ligand, can rapidly trigger or exacerbate psoriasis depending on the IL-23/IL-17 axis [227]. Nonsteroidal anti-inflammatory drugs inhibit the metabolism of arachidonic acid through the cycloxygenase pathway, contributing to the accumulation of leukotrienes, which have been postulated to exacerbate psoriasis [10].
Interestingly, psoriasis can also be triggered by biological agents, which is considered a paradoxical response. A study showed 216 reported cases of suspected TNF inhibitor-induced or -exacerbated psoriasis, which occurred more frequently with infliximab and was most prevalent in the first year of treatment for Crohn's disease and rheumatoid arthritis [228]. A retrospective analysis of patient with TNF inhibitor-induced psoriasis also yields consistent findings, indicating that infliximab is the predominant triggering agent, while Crohn's disease and rheumatoid arthritis are the most common primary conditions [229]. The paradoxical response may be associated with altered immunity induced by inhibiting TNF activity in predisposed individuals [14]. The pathogenesis is also thought to involve the IL-23/Th17 axis in the setting of TNF suppression [228].
One of the major unresolved mysteries is that psoriasis lesion often recur in the identical areas after the discontinuation of biologics targeting TNF-α, IL-23 and IL-17A/IL-17RA [230,231,232]. Currently, the most prevailing notion is that the existing biologics primarily serve to suppress the activities of pathogenic immune cells, rather than completely eliminating them [25].
Conclusions
This review provides a comprehensive discussion on the risk factors and underlying pathomechanism that contribute to the onset and recurrence of psoriasis. The development of psoriasis is complicated, likely caused by multiple triggering factors rather than a singular trigger. These triggering events could occur independently under different conditions or, alternatively, they exhibit accumulative or synergistic effects. It is therefore difficult to definitively attribute the disease to specific triggers. Though S. pyogenes infection has been widely acknowledged as a trigger for psoriasis, supported by a substantial body of research, triggers beyond S. pyogenes warrant further investigation to ascertain their role in initiating psoriasis.
Given that psoriasis is triggered by the environmental risk factors on a genetic basis, the disease prevention and management deserve due attention. A guideline on the risk assessment and disease management of psoriasis could be developed according to those clear triggering factors, which is helpful for the earlier diagnosis of mild or atypical cases and the precision management of psoriasis. For example, infection history (not only S. pyogenes infections but also other infections listed in this review), obesity and high blood lipid levels, excessive psychological stress, smoking, sleep disorder, a high-salt diet, and a history of taking specific medications should be considered as risk factors of psoriasis. From the patient's perspective, removing these risk factors is crucial for their personal management of the disease.
From a therapeutic point of view, patients may benefit from earlier treatments targeting the “beginning”, including but not exclusively antibiotic therapy, standardized probiotic supplementation, and anti-hyperlipidemia treatment, rather than solely focusing on treatments targeting the “pretermination”, such as the use of biological agents. Understanding the role of triggers in the pathogenesis of psoriasis would also provide clues to develop new therapies that target the triggering mechanisms during the onset and recurrence of psoriasis.
Availability of data and materials
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
Abbreviations
- KCs:
-
Keratinocytes
- DCs:
-
Dendritic cells
- Th:
-
T helper
- TLR:
-
Toll-like receptors
- IFN:
-
Interferon
- TNF:
-
Tumor necrosis factor
- IL:
-
Interleukin
- GWAS:
-
Genome-wide association studies
- TRM:
-
Tissue-resident memory T cells
- K17:
-
Keratin 17
- CLA + T cells:
-
Cutaneous lymphocyte-associated T cells
- PG:
-
Peptidoglycan
- PsA:
-
Psoriatic arthritis
- APCs:
-
Antigen-presenting cells
- RIG-I:
-
Retinoic acid inducible-gene I
- HIV:
-
Human Immunodeficiency Virus
- HPV:
-
Human papillomavirus
- SARS-CoV2:
-
Severe Acute Respiratory Syndrome Coronavirus 2
- NLRP1:
-
Nucleotide-binding domain and leucine-rich repeat pyrin domain-containing protein 1
- PRRs:
-
Pattern recognition receptors
- dsRNA:
-
Double-stranded RNA
- PASI:
-
Psoriasis Area and Severity Index
- AMPs:
-
Antimicrobial peptides
- F/B:
-
Firmicutes/Bacteroidetes
- FABP:
-
Fatty acid binding protein
- LPS:
-
Lipopolysaccharide
- LTA:
-
Lipoteichoic acid
- ET:
-
Endotoxins
- SCFAs:
-
Short-chain fatty acids
- Tregs:
-
Regulatory T cells
- MCFAs and LCFAs:
-
Middle-and long-chain fatty acids
- ILC3s:
-
Group 3 innate lymphoid cells
- FFAs:
-
Free fatty acids
- SFAs:
-
Saturated fatty acids
- PUFAs:
-
Polyunsaturated fatty acids
- LMs:
-
Lipid mediators
- LA:
-
Linoleic acid
- ALA:
-
α-Linolenic acid
- LC–MS/MS:
-
Liquid chromatography-tandem mass spectrometry
- SPMs:
-
Specialized pro-resolving lipid mediators
- Lxs:
-
Lipoxins
- Rvs:
-
Resolvins
- PDs:
-
Protectins
- MaRs:
-
Maresins
- RvD1:
-
Resolving D1
- RvD5:
-
Resolving D5
- PD1:
-
Protectin D1
- AT-LXA4 & AT-LXB4:
-
Aspirin-triggered forms of Lipoxin A4 and Lipoxin B4
- ROS:
-
Reactive oxygen species
- MUFAs:
-
Monounsaturated fatty acids
- Fer-1:
-
Ferrostatin-1
- ER:
-
Endoplasmic reticulum
- PLA2:
-
Phospholipase A2
- PLA2G4D:
-
PLA2 group IVD
- HPA:
-
Hypothalamic–pituitary–adrenal
- CRH:
-
Corticotropin-releasing hormone
- ACTH:
-
Adrenocorticotrophic hormone
- VEGF:
-
Vascular endothelial growth factor
- MCs:
-
Mast cells
- NT:
-
Neurotensin
- SP:
-
Substance P
- NGF:
-
Nerve growth factor
- PACAP:
-
Pituitary adenylate cyclase-activating polypeptide
- Erα:
-
Estrogen receptors α
- Erβ:
-
Estrogen receptors β
- IMQ:
-
Imiquimod
- PR:
-
Progesterone receptor
- ADT:
-
Androgen deprivation therapy
- PCa:
-
Prostate cancer
- KP:
-
Koebner phenomenon
- ssRNA:
-
Single-stranded RNA
- pDCs:
-
Plasmacytoid DCs
- cDCs:
-
Conventional DCs
- NaCl:
-
Sodium chloride
- NFAT5:
-
Nuclear factor of activated T cells 5
- SGK1:
-
Serum/glucocorticoid-regulated kinase 1
- PD-1:
-
Programmed cell death protein 1
- PD-L1:
-
Programmed death-ligand 1
References
Afonina IS, Van Nuffel E, Beyaert R. Immune responses and therapeutic options in psoriasis. Cell Mol Life Sci. 2021;78(6):2709–27.
Tokuyama M, Mabuchi T. New treatment addressing the pathogenesis of psoriasis. Int J Mol Sci. 2020;21(20):7488.
Sticherling M. Psoriasis and autoimmunity. Autoimmun Rev. 2016;15(12):1167–70.
Vojdani A. A potential link between environmental triggers and autoimmunity. Autoimmune Dis. 2014;2014:437231.
Teng Y, Xie W, Tao X, Liu N, Yu Y, Huang Y, et al. Infection-provoked psoriasis: Induced or aggravated (Review). Exp Ther Med. 2021;21(6):567.
Griffiths CEM, Armstrong AW, Gudjonsson JE, Barker J. Psoriasis. Lancet. 2021;397(10281):1301–15.
Gazel U, Ayan G, Solmaz D, Akar S, Aydin SZ. The impact of smoking on prevalence of psoriasis and psoriatic arthritis. Rheumatology (Oxford). 2020;59(10):2695–710.
Yang YW, Kang JH, Lin HC. Increased risk of psoriasis following obstructive sleep apnea: a longitudinal population-based study. Sleep Med. 2012;13(3):285–9.
Passali M, Josefsen K, Frederiksen JL, Antvorskov JC. Current evidence on the efficacy of gluten-free diets in multiple sclerosis, psoriasis, type 1 diabetes and autoimmune thyroid diseases. Nutrients. 2020;12(8):2316.
Fry L, Baker BS. Triggering psoriasis: the role of infections and medications. Clin Dermatol. 2007;25(6):606–15.
Kim GK, Del Rosso JQ. Drug-provoked psoriasis: is it drug induced or drug aggravated?: understanding pathophysiology and clinical relevance. J Clin Aesthet Dermatol. 2010;3(1):32–8.
Jacobi TC, Highet A. A clinical dilemma while treating hypercholesterolaemia in psoriasis. Br J Dermatol. 2003;149(6):1305–6.
Voudouri D, Nikolaou V, Laschos K, Charpidou A, Soupos N, Triantafyllopoulou I, et al. Anti-PD1/PDL1 induced psoriasis. Curr Probl Cancer. 2017;41(6):407–12.
Sfikakis PP, Iliopoulos A, Elezoglou A, Kittas C, Stratigos A. Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction. Arthritis Rheum. 2005;52(8):2513–8.
Taylor C, Burns DA, Wiselka MJ. Extensive psoriasis induced by interferon alfa treatment for chronic hepatitis C. Postgrad Med J. 2000;76(896):365–7.
Isler MF, Coates SJ, Boos MD. Climate change, the cutaneous microbiome and skin disease: implications for a warming world. Int J Dermatol. 2022;62(3):337–45.
Bellinato F, Adami G, Vaienti S, Benini C, Gatti D, Idolazzi L, et al. Association between short-term exposure to environmental air pollution and psoriasis flare. JAMA Dermatol. 2022;158(4):375–81.
Le ST, Toussi A, Maverakis N, Marusina AI, Barton VR, Merleev AA, et al. The cutaneous and intestinal microbiome in psoriatic disease. Clin Immunol. 2020;218:108537.
De Pessemier B, Grine L, Debaere M, Maes A, Paetzold B, Callewaert C. Gut-skin axis: current knowledge of the interrelationship between microbial dysbiosis and skin conditions. Microorganisms. 2021;9(2):353.
Stewart TJ, Tong W, Whitfeld MJ. The associations between psychological stress and psoriasis: a systematic review. Int J Dermatol. 2018;57(11):1275–82.
Gui XY, Yu XL, Jin HZ, Zuo YG, Wu C. Prevalence of metabolic syndrome in Chinese psoriasis patients: a hospital-based cross-sectional study. J Diabetes Investig. 2018;9(1):39–43.
Hellberg S, Raffetseder J, Rundquist O, Magnusson R, Papapavlou G, Jenmalm MC, et al. Progesterone Dampens Immune Responses in In Vitro Activated CD4(+) T Cells and Affects Genes Associated With Autoimmune Diseases That Improve During Pregnancy. Front Immunol. 2021;12:672168.
Tokura Y, Phadungsaksawasdi P, Kurihara K, Fujiyama T, Honda T. Pathophysiology of Skin Resident Memory T Cells. Front Immunol. 2020;11:618897.
Dong C, Lin L, Du J. Characteristics and sources of tissue-resident memory T cells in psoriasis relapse. Curr Res Immunol. 2023;4:100067.
Tian D, Lai Y. The relapse of psoriasis: mechanisms and mysteries. JID Innovations. 2022;2(3):100116.
Puig L, Costanzo A, Muñoz-Elías EJ, Jazra M, Wegner S, Paul CF, et al. The biological basis of disease recurrence in psoriasis: a historical perspective and current models. Br J Dermatol. 2022;186(5):773–81.
Thorleifsdottir RH, Eysteinsdóttir JH, Olafsson JH, Sigurdsson MI, Johnston A, Valdimarsson H, et al. Throat Infections are associated with exacerbation in a substantial proportion of patients with chronic plaque psoriasis. Acta Derm Venereol. 2016;96(6):788–91.
Ng CY, Huang YH, Chu CF, Wu TC, Liu SH. Risks for Staphylococcus aureus colonization in patients with psoriasis: a systematic review and meta-analysis. Br J Dermatol. 2017;177(4):967–77.
Arabatzis M, Velegraki A. Evidence for the presence of a human saprophytic oral bacterium, Mycoplasma faucium, in the skin lesions of a psoriatic patient. J Cutan Pathol. 2022;49(5):463–7.
Moen K, Brun JG, Valen M, Skartveit L, Eribe EK, Olsen I, et al. Synovial inflammation in active rheumatoid arthritis and psoriatic arthritis facilitates trapping of a variety of oral bacterial DNAs. Clin Exp Rheumatol. 2006;24(6):656–63.
Cheng WC, van Asten SD, Burns LA, Evans HG, Walter GJ, Hashim A, et al. Periodontitis-associated pathogens P. gingivalis and A. actinomycetemcomitans activate human CD14(+) monocytes leading to enhanced Th17/IL-17 responses. Eur J Immunol. 2016;46(9):2211–21.
Yu M, Zhang R, Ni P, Chen S, Duan G. Helicobacter pylori infection and psoriasis: a systematic review and meta-analysis. Medicina (Kaunas). 2019;55(10):645.
Stinco G, Fabris M, Pasini E, Pontarini E, Patriarca MM, Piccirillo F, et al. Detection of DNA of Chlamydophila psittaci in subjects with psoriasis: a casual or a causal link? Br J Dermatol. 2012;167(4):926–8.
Morar N, Willis-Owen SA, Maurer T, Bunker CB. HIV-associated psoriasis: pathogenesis, clinical features, and management. Lancet Infect Dis. 2010;10(7):470–8.
Chen ML, Kao WM, Huang JY, Hung YM, Wei JC. Human papillomavirus infection associated with increased risk of new-onset psoriasis: a nationwide population-based cohort study. Int J Epidemiol. 2020;49(3):786–97.
Chun K, Afshar M, Audish D, Kabigting F, Paik A, Gallo R, et al. Hepatitis C may enhance key amplifiers of psoriasis. J Eur Acad Dermatol Venereol. 2017;31(4):672–8.
Garg G, Thami GP. Psoriasis Herpeticum due to Varicella Zoster Virus: a Kaposi’s Varicelliform Eruption in Erythrodermic Psoriasis. Indian J Dermatol. 2012;57(3):213–4.
Jiyad Z, Moriarty B, Creamer D, Higgins E. Generalized pustular psoriasis associated with Epstein-Barr virus. Clin Exp Dermatol. 2015;40(2):146–8.
Yazici AC, Aslan G, Baz K, Ikizoglu G, Api H, Serin MS, et al. A high prevalence of parvovirus B19 DNA in patients with psoriasis. Arch Dermatol Res. 2006;298(5):231–5.
Weitz M, Kiessling C, Friedrich M, Prösch S, Höflich C, Kern F, et al. Persistent CMV infection correlates with disease activity and dominates the phenotype of peripheral CD8+ T cells in psoriasis. Exp Dermatol. 2011;20(7):561–7.
Yoneda K, Matsuoka-Shirahige Y, Demitsu T, Kubota Y. Pustular psoriasis precipitated by cytomegalovirus infection. Br J Dermatol. 2012;167(5):1186–9.
Paniz Mondolfi AE, Hernandez Perez M, Blohm G, Marquez M, Mogollon Mendoza A, Hernandez-Pereira CE, et al. Generalized pustular psoriasis triggered by Zika virus infection. Clin Exp Dermatol. 2018;43(2):171–4.
Korzhova TP, Shyrobokov VP, Koliadenko VH, Korniushenko OM, Akhramieieva NV, Stepanenko VI. Coxsackie B viral infection in the etiology and clinical pathogenesis of psoriasis. Lik Sprava. 2001;3:54–8.
Molès JP, Tesniere A, Guilhou JJ. A new endogenous retroviral sequence is expressed in skin of patients with psoriasis. Br J Dermatol. 2005;153(1):83–9.
Seetharam KA, Sridevi K. Chikungunya infection: a new trigger for psoriasis. J Dermatol. 2011;38(10):1033–4.
Kutlu Ö, Metin A. A case of exacerbation of psoriasis after oseltamivir and hydroxychloroquine in a patient with COVID-19: Will cases of psoriasis increase after COVID-19 pandemic? Dermatol Ther. 2020;33(4):e13383.
de Jesús-Gil C, Sans-de San Nicolàs L, Ruiz-Romeu E, Ferran M, Soria-Martínez L, García-Jiménez I, et al. Interplay between Humoral and CLA(+) T Cell Response against Candida albicans in Psoriasis. Int J Mol Sci. 2021;22(4):1519.
Park CO, Fu X, Jiang X, Pan Y, Teague JE, Collins N, et al. Staged development of long-lived T-cell receptor αβ T(H)17 resident memory T-cell population to Candida albicans after skin infection. J Allergy Clin Immunol. 2018;142(2):647–62.
Rudramurthy SM, Honnavar P, Chakrabarti A, Dogra S, Singh P, Handa S. Association of Malassezia species with psoriatic lesions. Mycoses. 2014;57(8):483–8.
Telfer NR, Chalmers RJ, Whale K, Colman G. The role of streptococcal infection in the initiation of guttate psoriasis. Arch Dermatol. 1992;128(1):39–42.
Haapasalo K, Koskinen LLE, Suvilehto J, Jousilahti P, Wolin A, Suomela S, et al. The Psoriasis Risk Allele HLA-C*06:02 Shows Evidence of Association with Chronic or Recurrent Streptococcal Tonsillitis. Infect Immun. 2018;86(10):e00304-18.
Mallbris L, Wolk K, Sánchez F, Ståhle M. HLA-Cw*0602 associates with a twofold higher prevalence of positive streptococcal throat swab at the onset of psoriasis: a case control study. BMC Dermatol. 2009;9:5.
Groot J, Blegvad C, Nybo Andersen AM, Zachariae C, Skov L. Tonsillitis and pediatric psoriasis: Cohort and cross-sectional analyses of offspring from the Danish National Birth Cohort. J Am Acad Dermatol. 2020;82(3):666–74.
Diluvio L, Vollmer S, Besgen P, Ellwart JW, Chimenti S, Prinz JC. Identical TCR beta-chain rearrangements in streptococcal angina and skin lesions of patients with psoriasis vulgaris. J Immunol. 2006;176(11):7104–11.
Chen ML, Ku YH, Yip HT, Wei JC. Tonsillectomy and the subsequent risk of psoriasis: a nationwide population-based cohort study. J Am Acad Dermatol. 2021;85(6):1493–502.
Thorleifsdottir RH, Sigurdardottir SL, Sigurgeirsson B, Olafsson JH, Sigurdsson MI, Petersen H, et al. Improvement of psoriasis after tonsillectomy is associated with a decrease in the frequency of circulating T cells that recognize streptococcal determinants and homologous skin determinants. J Immunol (Baltimore, Md : 1950). 2012;188(10):5160–5.
Rachakonda TD, Dhillon JS, Florek AG, Armstrong AW. Effect of tonsillectomy on psoriasis: a systematic review. J Am Acad Dermatol. 2015;72(2):261–75.
Owen CM, Chalmers R, O’Sullivan T, Griffiths CE. WITHDRAWN: Antistreptococcal interventions for guttate and chronic plaque psoriasis. Cochrane Database Syst Rev. 2019;3(3):Cd001976.
Garritsen FM, Kraag DE, de Graaf M. Guttate psoriasis triggered by perianal streptococcal infection. Clin Exp Dermatol. 2017;42(5):536–8.
Johnston A, Gudjonsson JE, Sigmundsdottir H, Love TJ, Valdimarsson H. Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8(+) T cells. Clin Exp Immunol. 2004;138(1):83–93.
Yunusbaeva M, Valiev R, Bilalov F, Sultanova Z, Sharipova L, Yunusbayev B. Psoriasis patients demonstrate HLA-Cw*06:02 allele dosage-dependent T cell proliferation when treated with hair follicle-derived keratin 17 protein. Sci Rep. 2018;8(1):6098.
de Jesús-Gil C, Sans-de SanNicolàs L, García-Jiménez I, Ferran M, Celada A, Chiriac A, et al. The translational relevance of human circulating memory cutaneous lymphocyte-associated antigen positive T cells in inflammatory skin disorders. Front Immunol. 2021;12:652613.
Leung DY, Gately M, Trumble A, Ferguson-Darnell B, Schlievert PM, Picker LJ. Bacterial superantigens induce T cell expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen, via stimulation of interleukin 12 production. J Exp Med. 1995;181(2):747–53.
Ruiz-Romeu E, Ferran M, Sagristà M, Gómez J, Giménez-Arnau A, Herszenyi K, et al. Streptococcus pyogenes-induced cutaneous lymphocyte antigen-positive T cell-dependent epidermal cell activation triggers TH17 responses in patients with guttate psoriasis. J Allergy Clin Immunol. 2016;138(2):491-9.e6.
De Jesús-Gil C, Ruiz-Romeu E, Ferran M, Chiriac A, Deza G, Hóllo P, et al. CLA(+) T Cell Response to Microbes in Psoriasis. Front Immunol. 2018;9:1488.
Ruiz-Romeu E, Ferran M, de Jesús-Gil C, García P, Sagristà M, Casanova JM, et al. Microbe-Dependent Induction of IL-9 by CLA(+) T Cells in Psoriasis and Relationship with IL-17A. J Invest Dermatol. 2018;138(3):580–7.
Baker BS, Laman JD, Powles A, van der Fits L, Voerman JS, Melief MJ, et al. Peptidoglycan and peptidoglycan-specific Th1 cells in psoriatic skin lesions. J Pathol. 2006;209(2):174–81.
Baker BS, Powles A, Fry L. Peptidoglycan: a major aetiological factor for psoriasis? Trends Immunol. 2006;27(12):545–51.
Ajib R, Janbazian L, Rahal E, Matar GM, Zaynoun S, Kibbi AG, et al. HLA allele associations and V-beta T-lymphocyte expansions in patients with psoriasis, harboring toxin-producing Staphylococcus aureus. J Biomed Biotechnol. 2005;2005(4):310–5.
Travers JB, Hamid QA, Norris DA, Kuhn C, Giorno RC, Schlievert PM, et al. Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis. J Clin Invest. 1999;104(9):1181–9.
Tomi NS, Kränke B, Aberer E. Staphylococcal toxins in patients with psoriasis, atopic dermatitis, and erythroderma, and in healthy control subjects. J Am Acad Dermatol. 2005;53(1):67–72.
Han JH, Park JW, Han KD, Park JB, Kim M, Lee JH. Smoking and Periodontitis Can Play a Synergistic Role in the Development of Psoriasis: A Nationwide Cohort Study. Dermatology. 2022;238(3):554–61.
Zhang X, Gu H, Xie S, Su Y. Periodontitis in patients with psoriasis: a systematic review and meta-analysis. Oral Dis. 2022;28(1):33–43.
Moutsopoulos NM, Kling HM, Angelov N, Jin W, Palmer RJ, Nares S, et al. Porphyromonas gingivalis promotes Th17 inducing pathways in chronic periodontitis. J Autoimmun. 2012;39(4):294–303.
Zhu H, Lou F, Yin Q, Gao Y, Sun Y, Bai J, et al. RIG-I antiviral signaling drives interleukin-23 production and psoriasis-like skin disease. EMBO Mol Med. 2017;9(5):589–604.
Yen YF, Chuang PH, Jen IA, Chen M, Lan YC, Liu YL, et al. Incidence of autoimmune diseases in a nationwide HIV/AIDS patient cohort in Taiwan, 2000–2012. Ann Rheum Dis. 2017;76(4):661–5.
Fuchs D, Hausen A, Reibnegger G, Werner ER, Dierich MP, Wachter H. Psoriasis, gamma-interferon, and the acquired immunodeficiency syndrome. Ann Intern Med. 1987;106(1):165.
Namazi MR. Paradoxical exacerbation of psoriasis in AIDS: proposed explanations including the potential roles of substance P and gram-negative bacteria. Autoimmunity. 2004;37(1):67–71.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China Lancet. 2020;395(10223):497–506.
Buhl T, Beissert S, Gaffal E, Goebeler M, Hertl M, Mauch C, et al. COVID-19 and implications for dermatological and allergological diseases. J Dtsch Dermatol Ges. 2020;18(8):815–24.
Bellinato F, Maurelli M, Gisondi P, Girolomoni G. Cutaneous Adverse Reactions Associated with SARS-CoV-2 Vaccines. J Clin Med. 2021;10(22):5344.
Bauernfried S, Scherr MJ, Pichlmair A, Duderstadt KE, Hornung V. Human NLRP1 is a sensor for double-stranded RNA. Science. 2021;371(6528):eabd0811.
Fetter T, de Graaf DM, Claus I, Wenzel J. Aberrant inflammasome activation as a driving force of human autoimmune skin disease. Front Immunol. 2023;14:1190388.
Sand J, Haertel E, Biedermann T, Contassot E, Reichmann E, French LE, et al. Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes. Cell Death Dis. 2018;9(2):24.
Ekman A-K, Verma D, Fredrikson M, Bivik C, Enerbäck C. Genetic variations of NLRP1: susceptibility in psoriasis. Br J Dermatol. 2014;171(6):1517–20.
Tibble R, Yonemitsu MA, Mitchell PS. Stalled but not forgotten: Bacterial exotoxins inhibit translation to activate NLRP1. J Exp Med. 2023;220(10):e20231160.
Fry L, Baker BS, Powles AV, Fahlen A, Engstrand L. Is chronic plaque psoriasis triggered by microbiota in the skin? Br J Dermatol. 2013;169(1):47–52.
Leung DY, Walsh P, Giorno R, Norris DA. A potential role for superantigens in the pathogenesis of psoriasis. J Invest Dermatol. 1993;100(3):225–8.
Onsun N, Arda Ulusal H, Su O, Beycan I, Biyik Ozkaya D, Senocak M. Impact of Helicobacter pylori infection on severity of psoriasis and response to treatment. Eur J Dermatol. 2012;22(1):117–20.
Yamaoka Y, Kita M, Kodama T, Sawai N, Kashima K, Imanishi J. Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains. Gut. 1997;41(4):442–51.
Campanati A, Ganzetti G, Martina E, Giannoni M, Gesuita R, Bendia E, et al. Helicobacter pylori infection in psoriasis: results of a clinical study and review of the literature. Int J Dermatol. 2015;54(5):e109–14.
Quan C, Chen XY, Li X, Xue F, Chen LH, Liu N, et al. Psoriatic lesions are characterized by higher bacterial load and imbalance between Cutibacterium and Corynebacterium. J Am Acad Dermatol. 2020;82(4):955–61.
Yerushalmi M, Elalouf O, Anderson M, Chandran V. The skin microbiome in psoriatic disease: a systematic review and critical appraisal. J Transl Autoimmun. 2019;2:100009.
Fahlén A, Engstrand L, Baker BS, Powles A, Fry L. Comparison of bacterial microbiota in skin biopsies from normal and psoriatic skin. Arch Dermatol Res. 2012;304(1):15–22.
Langan EA, Künstner A, Miodovnik M, Zillikens D, Thaçi D, Baines JF, et al. Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis. Br J Dermatol. 2019;181(6):1254–64.
Alekseyenko AV, Perez-Perez GI, De Souza A, Strober B, Gao Z, Bihan M, et al. Community differentiation of the cutaneous microbiota in psoriasis. Microbiome. 2013;1(1):31.
Kong HH, Andersson B, Clavel T, Common JE, Jackson SA, Olson ND, et al. Performing skin microbiome research: a method to the madness. J Invest Dermatol. 2017;137(3):561–8.
Ridaura VK, Bouladoux N, Claesen J, Chen YE, Byrd AL, Constantinides MG, et al. Contextual control of skin immunity and inflammation by Corynebacterium. J Exp Med. 2018;215(3):785–99.
Cai Y, Xue F, Quan C, Qu M, Liu N, Zhang Y, et al. A critical role of the IL-1β-IL-1R signaling pathway in skin inflammation and psoriasis pathogenesis. J Invest Dermatol. 2019;139(1):146–56.
Tett A, Pasolli E, Farina S, Truong DT, Asnicar F, Zolfo M, et al. Unexplored diversity and strain-level structure of the skin microbiome associated with psoriasis. NPJ Biofilms Microbiomes. 2017;3:14.
Chang HW, Yan D, Singh R, Liu J, Lu X, Ucmak D, et al. Alteration of the cutaneous microbiome in psoriasis and potential role in Th17 polarization. Microbiome. 2018;6(1):154.
Shklovskaya E, O’Sullivan BJ, Ng LG, Roediger B, Thomas R, Weninger W, et al. Langerhans cells are precommitted to immune tolerance induction. Proc Natl Acad Sci U S A. 2011;108(44):18049–54.
Zanvit P, Konkel JE, Jiao X, Kasagi S, Zhang D, Wu R, et al. Antibiotics in neonatal life increase murine susceptibility to experimental psoriasis. Nat Commun. 2015;6:8424.
Polak K, Bergler-Czop B, Szczepanek M, Wojciechowska K, Frątczak A, Kiss N. Psoriasis and Gut Microbiome-Current State of Art. Int J Mol Sci. 2021;22(9):4529.
Todberg T, Egeberg A, Zachariae C, Sørensen N, Pedersen O, Skov L. Patients with psoriasis have a dysbiotic taxonomic and functional gut microbiota. Br J Dermatol. 2022;187:89–98.
Hidalgo-Cantabrana C, Gómez J, Delgado S, Requena-López S, Queiro-Silva R, Margolles A, et al. Gut microbiota dysbiosis in a cohort of patients with psoriasis. Br J Dermatol. 2019;181(6):1287–95.
Huang L, Gao R, Yu N, Zhu Y, Ding Y, Qin H. Dysbiosis of gut microbiota was closely associated with psoriasis. Sci China Life Sci. 2019;62(6):807–15.
Sikora M, Stec A, Chrabaszcz M, Waskiel-Burnat A, Zaremba M, Olszewska M, et al. Intestinal fatty acid binding protein, a biomarker of intestinal barrier, is associated with severity of psoriasis. J Clin Med. 2019;8(7):1021.
Mu Q, Kirby J, Reilly CM, Luo XM. Leaky gut as a danger signal for autoimmune diseases. Front Immunol. 2017;8:598.
Potgieter M, Bester J, Kell DB, Pretorius E. The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol Rev. 2015;39(4):567–91.
Ramírez-Boscá A, Navarro-López V, Martínez-Andrés A, Such J, Francés R, de Horgala Parte J, et al. Identification of Bacterial DNA in the Peripheral Blood of Patients With Active Psoriasis. JAMA Dermatol. 2015;151(6):670–1.
Codoñer FM, Ramírez-Bosca A, Climent E, Carrión-Gutierrez M, Guerrero M, Pérez-Orquín JM, et al. Gut microbial composition in patients with psoriasis. Sci Rep. 2018;8(1):3812.
Visser MJE, Kell DB, Pretorius E. Bacterial dysbiosis and translocation in psoriasis vulgaris. Front Cell Infect Microbiol. 2019;9:7.
Kell DB, Pretorius E. No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases. Biol Rev Camb Philos Soc. 2018;93(3):1518–57.
Ely PH. Is psoriasis a bowel disease? Successful treatment with bile acids and bioflavonoids suggests it is. Clin Dermatol. 2018;36(3):376–89.
Schönfeld P, Wojtczak L. Short- and medium-chain fatty acids in energy metabolism: the cellular perspective. J Lipid Res. 2016;57(6):943–54.
D’Orsogna LJ, Roelen DL, Doxiadis II, Claas FH. Alloreactivity from human viral specific memory T-cells. Transpl Immunol. 2010;23(4):149–55.
Mardinoglu A, Wu H, Bjornson E, Zhang C, Hakkarainen A, Räsänen SM, et al. An Integrated understanding of the rapid metabolic benefits of a carbohydrate-restricted diet on hepatic steatosis in humans. Cell Metab. 2018;27(3):559-71.e5.
Kinoshita M, Kayama H, Kusu T, Yamaguchi T, Kunisawa J, Kiyono H, et al. Dietary folic acid promotes survival of Foxp3+ regulatory T cells in the colon. J Immunol (Baltimore, Md : 1950). 2012;189(6):2869–78.
Mellor AL, Lemos H, Huang L. Indoleamine 2,3-Dioxygenase and Tolerance: Where Are We Now? Front Immunol. 2017;8:1360.
Melo-Gonzalez F, Hepworth MR. Functional and phenotypic heterogeneity of group 3 innate lymphoid cells. Immunology. 2017;150(3):265–75.
Ward NL, Umetsu DT. A new player on the psoriasis block: IL-17A- and IL-22-producing innate lymphoid cells. J Invest Dermatol. 2014;134(9):2305–7.
Mirpuri J. The emerging role of group 3 innate lymphoid cells in the neonate: interaction with the maternal and neonatal microbiome. Oxf Open Immunol. 2021;2(1):iqab009.
Macfarlane S, Macfarlane GT. Regulation of short-chain fatty acid production. Proc Nutr Soc. 2003;62(1):67–72.
Chun E, Lavoie S, Fonseca-Pereira D, Bae S, Michaud M, Hoveyda HR, et al. Metabolite-sensing receptor ffar2 regulates colonic group 3 innate lymphoid cells and gut immunity. Immunity. 2019;51(5):871-84.e6.
Kim SH, Cho BH, Kiyono H, Jang YS. Microbiota-derived butyrate suppresses group 3 innate lymphoid cells in terminal ileal Peyer’s patches. Sci Rep. 2017;7(1):3980.
Chen YH, Wu CS, Chao YH, Lin CC, Tsai HY, Li YR, et al. Lactobacillus pentosus GMNL-77 inhibits skin lesions in imiquimod-induced psoriasis-like mice. J Food Drug Anal. 2017;25(3):559–66.
Szántó M, Dózsa A, Antal D, Szabó K, Kemény L, Bai P. Targeting the gut-skin axis-Probiotics as new tools for skin disorder management? Exp Dermatol. 2019;28(11):1210–8.
Selvanderan SP, Goldblatt F, Nguyen NQ, Costello SP. Faecal microbiota transplantation for Clostridium difficile infection resulting in a decrease in psoriatic arthritis disease activity. Clin Exp Rheumatol. 2019;37(3):514–5.
Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and obesity: a systematic review and meta-analysis of observational studies. Nutr Diabetes. 2012;2(12):e54.
Stolarczyk E. Adipose tissue inflammation in obesity: a metabolic or immune response? Curr Opin Pharmacol. 2017;37:35–40.
Tsigalou C, Vallianou N, Dalamaga M. Autoantibody production in obesity: is there evidence for a link between obesity and autoimmunity? Curr Obes Rep. 2020;9(3):245–54.
Gao Y, Yi X, Ding Y. Combined transcriptomic analysis revealed AKR1B10 played an important role in psoriasis through the dysregulated lipid pathway and Overproliferation of Keratinocyte. Biomed Res Int. 2017;2017:8717369.
Herbert D, Franz S, Popkova Y, Anderegg U, Schiller J, Schwede K, et al. High-fat diet exacerbates early psoriatic skin inflammation independent of obesity: saturated fatty acids as key players. J Invest Dermatol. 2018;138(9):1999–2009.
Stelzner K, Herbert D, Popkova Y, Lorz A, Schiller J, Gericke M, et al. Free fatty acids sensitize dendritic cells to amplify TH1/TH17-immune responses. Eur J Immunol. 2016;46(8):2043–53.
Zhang Y, Li Q, Rao E, Sun Y, Grossmann Michael E, Morris Rebecca J, et al. Epidermal Fatty Acid Binding Protein Promotes Skin Inflammation Induced by High-Fat Diet. Immunity. 2015;42(5):953–64.
Tsoukalas D, Fragoulakis V, Sarandi E, Docea AO, Papakonstaninou E, Tsilimidos G, et al. Targeted metabolomic analysis of serum fatty acids for the prediction of autoimmune diseases. Front Mol Biosci. 2019;6:120.
Nakamizo S, Honda T, Kabashima K. Saturated Fatty Acids as Possible Key Amplifiers of Psoriatic Dermatitis. J Invest Dermatol. 2018;138(9):1901–3.
Huang S, Rutkowsky JM, Snodgrass RG, Ono-Moore KD, Schneider DA, Newman JW, et al. Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. J Lipid Res. 2012;53(9):2002–13.
Snodgrass RG, Huang S, Choi IW, Rutledge JC, Hwang DH. Inflammasome-mediated secretion of IL-1β in human monocytes through TLR2 activation; modulation by dietary fatty acids. J Immunol. 2013;191(8):4337–47.
Endo Y, Yokote K, Nakayama T. The obesity-related pathology and Th17 cells. Cell Mol Life Sci. 2017;74(7):1231–45.
Pan Y, Tian T, Park CO, Lofftus SY, Mei S, Liu X, et al. Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. Nature. 2017;543(7644):252–6.
Haghikia A, Jörg S, Duscha A, Berg J, Manzel A, Waschbisch A, et al. Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity. 2015;43(4):817–29.
Simard M, Morin S, Ridha Z, Pouliot R. Current knowledge of the implication of lipid mediators in psoriasis. Front Immunol. 2022;13:961107.
Basil MC, Levy BD. Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Nat Rev Immunol. 2016;16(1):51–67.
Serhan CN. Resolution phase of inflammation: novel endogenous anti-inflammatory and Proresolving lipid mediators and pathways. Annu Rev Immunol. 2007;25(1):101–37.
Sorokin AV, Domenichiello AF, Dey AK, Yuan ZX, Goyal A, Rose SM, et al. Bioactive lipid mediator profiles in human psoriasis skin and blood. J Invest Dermatol. 2018;138(7):1518–28.
Sorokin AV, Norris PC, English JT, Dey AK, Chaturvedi A, Baumer Y, et al. Identification of proresolving and inflammatory lipid mediators in human psoriasis. J Clin Lipidol. 2018;12(4):1047–60.
Stockwell BR. Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications. Cell. 2022;185(14):2401–21.
Tsurusaki S, Tsuchiya Y, Koumura T, Nakasone M, Sakamoto T, Matsuoka M, et al. Hepatic ferroptosis plays an important role as the trigger for initiating inflammation in nonalcoholic steatohepatitis. Cell Death Dis. 2019;10(6):449.
Shou Y, Yang L, Yang Y, Xu J. Inhibition of keratinocyte ferroptosis suppresses psoriatic inflammation. Cell Death Dis. 2021;12(11):1009.
Zhou Q, Yang L, Li T, Wang K, Huang X, Shi J, et al. Mechanisms and inhibitors of ferroptosis in psoriasis. Front Mol Biosci. 2022;9:1019447.
Cnop M, Ladriere L, Hekerman P, Ortis F, Cardozo AK, Dogusan Z, et al. Selective inhibition of eukaryotic translation initiation factor 2 alpha dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic beta-cell dysfunction and apoptosis. J Biol Chem. 2007;282(6):3989–97.
Brookheart RT, Michel CI, Schaffer JE. As a matter of fat. Cell Metab. 2009;10(1):9–12.
Bagchi S, Genardi S, Wang CR. Linking CD1-Restricted T Cells With Autoimmunity and Dyslipidemia: Lipid Levels Matter. Front Immunol. 2018;9:1616.
Cheung KL, Jarrett R, Subramaniam S, Salimi M, Gutowska-Owsiak D, Chen YL, et al. Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a. J Exp Med. 2016;213(11):2399–412.
Bagchi S, He Y, Zhang H, Cao L, Van Rhijn I, Moody DB, et al. CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice. J Clin Invest. 2017;127(6):2339–52.
Rousset L, Halioua B. Stress and psoriasis. Int J Dermatol. 2018;57(10):1165–72.
Manolache L, Petrescu-Seceleanu D, Benea V. Life events involvement in psoriasis onset/recurrence. Int J Dermatol. 2010;49(6):636–41.
Snast I, Reiter O, Atzmony L, Leshem YA, Hodak E, Mimouni D, et al. Psychological stress and psoriasis: a systematic review and meta-analysis. Br J Dermatol. 2018;178(5):1044–55.
Woźniak E, Owczarczyk-Saczonek A, Placek W. Psychological stress, mast cells, and psoriasis-is there any relationship? Int J Mol Sci. 2021;22(24):13252.
Dai YX, Tai YH, Chang YT, Chen TJ, Chen MH. Association between major depressive disorder and subsequent autoimmune skin diseases: a nationwide population-based cohort study. J Affect Disord. 2020;274:334–8.
Chou YJ, Tai YH, Dai YX, Lee DD, Chang YT, Chen TJ, et al. Obsessive-compulsive disorder and the associated risk of autoimmune skin diseases: a nationwide population-based cohort study. CNS Spectr. 2022;28(2):157–63.
Dai YX, Tai YH, Chang YT, Chen TJ, Chen MH. Posttraumatic stress disorder and the associated risk of autoimmune skin diseases: a nationwide population-based cohort study. Psychosom Med. 2021;83(3):212–7.
Nevriana A, Pierce M, Abel KM, Rossides M, Wicks S, Dalman C, et al. Association between parental mental illness and autoimmune diseases in the offspring - a nationwide register-based cohort study in Sweden. J Psychiatr Res. 2022;151:122–30.
Uvais NA, Rakhesh SV, Afra TP, Hafi NAB, Razmi TM. Comorbid psoriasis-bipolar disorder successfully treated with apremilast: much more than a mere coincidence? Gen Psychiatr. 2020;33(3):e100181.
Nadeem A, Ahmad SF, El-Sherbeeny AM, Al-Harbi NO, Bakheet SA, Attia SM. Systemic inflammation in asocial BTBR T(+) tf/J mice predisposes them to increased psoriatic inflammation. Prog Neuropsychopharmacol Biol Psychiatry. 2018;83:8–17.
Werner MCF, Wirgenes KV, Shadrin A, Lunding SH, Rødevand L, Hjell G, et al. Immune marker levels in severe mental disorders: associations with polygenic risk scores of related mental phenotypes and psoriasis. Transl Psychiatry. 2022;12(1):38.
Kanda N, Watanabe S. Regulatory roles of sex hormones in cutaneous biology and immunology. J Dermatol Sci. 2005;38(1):1–7.
Zachary C, Fackler N, Juhasz M, Pham C, Mesinkovska NA. Catamenial dermatoses associated with autoimmune, inflammatory, and systemic diseases: A systematic review(,). Int J Womens Dermatol. 2019;5(5):361–7.
McCombe PA, Greer JM, Mackay IR. Sexual dimorphism in autoimmune disease. Curr Mol Med. 2009;9(9):1058–79.
Adachi A, Honda T. Regulatory Roles of Estrogens in Psoriasis. J Clin Med. 2022;11(16):4890.
Adachi A, Honda T, Egawa G, Kanameishi S, Takimoto R, Miyake T, et al. Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions. J Allergy Clin Immunol. 2022;150(4):909-19.e8.
Kanda N, Watanabe S. 17β-estradiol Inhibits the Production of Interferon-induced Protein of 10kDa by Human Keratinocytes. J Invest Dermatol. 2003;120(3):411–9.
Boyd AS, King LE Jr. Tamoxifen-induced remission of psoriasis. J Am Acad Dermatol. 1999;41(5 Pt 2):887–9.
Cemil BC, Cengiz FP, Atas H, Ozturk G, Canpolat F. Sex hormones in male psoriasis patients and their correlation with the Psoriasis Area and Severity Index. J Dermatol. 2015;42(5):500–3.
Iwano R, Iwashita N, Takagi Y, Fukuyama T. Estrogen receptor α activation aggravates imiquimod-induced psoriasis-like dermatitis in mice by enhancing dendritic cell interleukin-23 secretion. J Appl Toxicol. 2020;40(10):1353–61.
Kobayashi K, Chikazawa S, Chen Y, Suzuki S, Ichimasu N, Katagiri K. Oestrogen inhibits psoriasis-like dermatitis induced by imiquimod in mice in relation to increased IL-10 producing cells despite elevated expression of IL-22, IL-23, IL-17 mRNA. Exp Dermatol. 2023;32(2):203–9.
Murase JE, Chan KK, Garite TJ, Cooper DM, Weinstein GD. Hormonal effect on psoriasis in pregnancy and post partum. Arch Dermatol. 2005;141(5):601–6.
Im S, Lee ES, Kim W, Song J, Kim J, Lee M, et al. Expression of progesterone receptor in human keratinocytes. J Korean Med Sci. 2000;15(6):647–54.
Ziółkowska E, Biedka M, Zyromska A, Makarewicz R. Psoriasis exacerbation after hormonotherapy in prostate cancer patient-Case report. Rep Pract Oncol Radiother. 2010;15(4):103–6.
Liu JM, Yu CP, Chuang HC, Wu CT, Hsu RJ. Androgen deprivation therapy for prostate cancer and the risk of autoimmune diseases. Prostate Cancer Prostatic Dis. 2019;22(3):475–82.
Allam JP, Bunzek C, Schnell L, Heltzel M, Weckbecker L, Wilsmann-Theis D, et al. Low serum testosterone levels in male psoriasis patients correlate with disease severity. Eur J Dermatol. 2019;29(4):375–82.
Yu RX, Hui Y, Li CR. Köebner phenomenon induced by cupping therapy in a psoriasis patient. Dermatol Online J. 2013;19(6):18575.
Tang L, Liao Y, Xu J, Li C. Koebner phenomenon induced by cupping therapy in the unstable stage of psoriasis: a case report. Dermatol Ther. 2021;34(2):e14852.
Polat Ekinci A, Pehlivan G. Cupping therapy as alternative medicine turns into a trigger of disease via the Koebner phenomenon: a case report of Hijama-induced psoriasis and review of the literature. Dermatol Ther. 2020;33(6):e14264.
Zhang LJ. Type1 Interferons potential initiating factors linking skin wounds with psoriasis pathogenesis. Front Immunol. 2019;10:1440.
Gregorio J, Meller S, Conrad C, Di Nardo A, Homey B, Lauerma A, et al. Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. J Exp Med. 2010;207(13):2921–30.
Nestle FO, Conrad C, Tun-Kyi A, Homey B, Gombert M, Boyman O, et al. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med. 2005;202(1):135–43.
Morizane S, Yamasaki K, Mühleisen B, Kotol PF, Murakami M, Aoyama Y, et al. Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands. J Invest Dermatol. 2012;132(1):135–43.
Adase CA, Borkowski AW, Zhang LJ, Williams MR, Sato E, Sanford JA, et al. Non-coding Double-stranded RNA and Antimicrobial Peptide LL-37 Induce Growth Factor Expression from Keratinocytes and Endothelial Cells. J Biol Chem. 2016;291(22):11635–46.
Chen L, Shen Z. Tissue-resident memory T cells and their biological characteristics in the recurrence of inflammatory skin disorders. Cell Mol Immunol. 2020;17(1):64–75.
Okamoto T, Ogawa Y, Kinoshita M, Ihara T, Shimada S, Koizumi S, et al. Mechanical stretch-induced ATP release from keratinocytes triggers Koebner phenomenon in psoriasis. J Dermatol Sci. 2021;103(1):60–2.
Qiao P, Guo W, Ke Y, Fang H, Zhuang Y, Jiang M, et al. Mechanical stretch exacerbates psoriasis by stimulating keratinocyte proliferation and cytokine production. J Invest Dermatol. 2019;139(7):1470–9.
Furue K, Ito T, Tanaka Y, Yumine A, Hashimoto-Hachiya A, Takemura M, et al. Cyto/chemokine profile of in vitro scratched keratinocyte model: Implications of significant upregulation of CCL20, CXCL8 and IL36G in Koebner phenomenon. J Dermatol Sci. 2019;94(1):244–51.
Wei J, Zhu J, Xu H, Zhou D, Elder JT, Tsoi LC, et al. Alcohol consumption and smoking in relation to psoriasis: a Mendelian randomization study. Br J Dermatol. 2022;187:684–91.
Armstrong AW, Harskamp CT, Dhillon JS, Armstrong EJ. Psoriasis and smoking: a systematic review and meta-analysis. Br J Dermatol. 2014;170(2):304–14.
Lee EJ, Han KD, Han JH, Lee JH. Smoking and risk of psoriasis: a nationwide cohort study. J Am Acad Dermatol. 2017;77(3):573–5.
Hayran Y, Yalçın B. Smoking habits amongst patients with psoriasis and the effect of smoking on clinical and treatment-associated characteristics: a cross-sectional study. Int J Clin Pract. 2021;75(2):e13751.
Armstrong AW, Armstrong EJ, Fuller EN, Sockolov ME, Voyles SV. Smoking and pathogenesis of psoriasis: a review of oxidative, inflammatory and genetic mechanisms. Br J Dermatol. 2011;165(6):1162–8.
Wang J, Li X, Zhang P, Yang T, Liu N, Qin L, et al. CHRNA5 Is Overexpressed in Patients with Psoriasis and Promotes Psoriasis-Like Inflammation in Mouse Models. J Invest Dermatol. 2022;142:2978–87.
Pezzolo E, Naldi L. The relationship between smoking, psoriasis and psoriatic arthritis. Expert Rev Clin Immunol. 2019;15(1):41–8.
Näslund-Koch C, Vedel-Krogh S, Bojesen SE, Skov L. Smoking is an independent but not a causal risk factor for moderate to severe psoriasis: a Mendelian randomization study of 105,912 individuals. Front Immunol. 2023;14:1119144.
Choi EH, Brown BE, Crumrine D, Chang S, Man MQ, Elias PM, et al. Mechanisms by which psychologic stress alters cutaneous permeability barrier homeostasis and stratum corneum integrity. J Invest Dermatol. 2005;124(3):587–95.
Hirotsu C, Rydlewski M, Araújo MS, Tufik S, Andersen ML. Sleep loss and cytokines levels in an experimental model of psoriasis. PLoS One. 2012;7(11):e51183.
Terán-Pérez G, Arana-Lechuga Y, Esqueda-León E, Santana-Miranda R, Rojas-Zamorano J, Velázquez MJ. Steroid hormones and sleep regulation. Mini Rev Med Chem. 2012;12(11):1040–8.
Paus R, Theoharides TC, Arck PC. Neuroimmunoendocrine circuitry of the “brain-skin connection.” Trends Immunol. 2006;27(1):32–9.
Michaëlsson G, Gerdén B, Hagforsen E, Nilsson B, Pihl-Lundin I, Kraaz W, et al. Psoriasis patients with antibodies to gliadin can be improved by a gluten-free diet. Br J Dermatol. 2000;142(1):44–51.
Michaëlsson G, Ahs S, Hammarström I, Lundin IP, Hagforsen E. Gluten-free diet in psoriasis patients with antibodies to gliadin results in decreased expression of tissue transglutaminase and fewer Ki67+ cells in the dermis. Acta Derm Venereol. 2003;83(6):425–9.
Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature. 2013;496(7446):518–22.
Wu C, Yosef N, Thalhamer T, Zhu C, Xiao S, Kishi Y, et al. Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature. 2013;496(7446):513–7.
Brenaut E, Horreau C, Pouplard C, Barnetche T, Paul C, Richard MA, et al. Alcohol consumption and psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol. 2013;27(Suppl 3):30–5.
Murzaku EC, Bronsnick T, Rao BK. Diet in dermatology: Part II. Melanoma, chronic urticaria, and psoriasis. J Am Acad Dermatol. 2014;71(6):1053.e1-16.e16.
Poikolainen K, Karvonen J, Pukkala E. Excess mortality related to alcohol and smoking among hospital-treated patients with psoriasis. Arch Dermatol. 1999;135(12):1490–3.
Dai YX, Wang SC, Chou YJ, Chang YT, Chen TJ, Li CP, et al. Smoking, but not alcohol, is associated with risk of psoriasis in a Taiwanese population-based cohort study. J Am Acad Dermatol. 2019;80(3):727–34.
Yeung CK, Chan HH. Cutaneous adverse effects of lithium: epidemiology and management. Am J Clin Dermatol. 2004;5(1):3–8.
Ockenfels HM, Wagner SN, Keim-Maas C, Funk R, Nussbaum G, Goos M. Lithium and psoriasis: cytokine modulation of cultured lymphocytes and psoriatic keratinocytes by lithium. Arch Dermatol Res. 1996;288(4):173–8.
Hampton PJ, Jans R, Flockhart RJ, Parker G, Reynolds NJ. Lithium regulates keratinocyte proliferation via glycogen synthase kinase 3 and NFAT2 (nuclear factor of activated T cells 2). J Cell Physiol. 2012;227(4):1529–37.
Gill R, Mohammed F, Badyal R, Coates L, Erskine P, Thompson D, et al. High-resolution structure of myo-inositol monophosphatase, the putative target of lithium therapy. Acta Crystallogr D Biol Crystallogr. 2005;61(Pt 5):545–55.
O’Brien M, Koo J. The mechanism of lithium and beta-blocking agents in inducing and exacerbating psoriasis. J Drugs Dermatol. 2006;5(5):426–32.
Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, et al. Oncogenes and signal transduction. Cell. 1991;64(2):281–302.
Ockenfels HM, Nussbaum G, Schultewolter T, Mertins K, Wagner SN, Goos M. Tyrosine phosphorylation in psoriatic T cells is modulated by drugs that induce or improve psoriasis. Dermatology. 1995;191(3):217–25.
Bonigen J, Raynaud-Donzel C, Hureaux J, Kramkimel N, Blom A, Jeudy G, et al. Anti-PD1-induced psoriasis: a study of 21 patients. J Eur Acad Dermatol Venereol. 2017;31(5):e254–7.
Mayor Ibarguren A, Enrique EA, Diana PL, Ana C, Pedro HP. Apremilast for immune checkpoint inhibitor-induced psoriasis: a case series. JAAD Case Rep. 2021;11:84–9.
Tanaka R, Ichimura Y, Kubota N, Saito A, Nakamura Y, Ishitsuka Y, et al. Activation of CD8 T cells accelerates anti-PD-1 antibody-induced psoriasis-like dermatitis through IL-6. Commun Biol. 2020;3(1):571.
Wolf R, Lo SA. Is transglutaminase the mediator between antimalarial drugs and psoriasis? Int J Dermatol. 1997;36(1):10–3.
van der Fits L, Mourits S, Voerman JS, Kant M, Boon L, Laman JD, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol (Baltimore, Md : 1950). 2009;182(9):5836–45.
Brown G, Wang E, Leon A, Huynh M, Wehner M, Matro R, et al. Tumor necrosis factor-α inhibitor-induced psoriasis: Systematic review of clinical features, histopathological findings, and management experience. J Am Acad Dermatol. 2017;76(2):334–41.
Mazloom SE, Yan D, Hu JZ, Ya J, Husni ME, Warren CB, et al. TNF-α inhibitor-induced psoriasis: a decade of experience at the Cleveland Clinic. J Am Acad Dermatol. 2020;83(6):1590–8.
Griffiths CEM, Strober BE, van de Kerkhof P, Ho V, Fidelus-Gort R, Yeilding N, et al. Comparison of Ustekinumab and Etanercept for Moderate-to-Severe Psoriasis. N Engl J Med. 2010;362(2):118–28.
Chiu HY, Hui RC, Tsai TF, Chen YC, Chang Liao NF, Chen PH, et al. Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: An 8-year multicenter study. J Am Acad Dermatol. 2023;88(1):71–8.
Masson Regnault M, Konstantinou MP, Khemis A, Poulin Y, Bourcier M, Amelot F, et al. Early relapse of psoriasis after stopping brodalumab: a retrospective cohort study in 77 patients. J Eur Acad Dermatol Venereol. 2017;31(9):1491–6.
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This work was supported by the National Natural Science Foundation of China (No.82173423, No.81974475, No.82103731), Shenzhen Natural Science Foundation (Basic Research Project, No. JCYJ20190809103805589) and Shenzhen Nanshan District Science and Technology Project (Key Project, No.2019003).
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M.H. and H.C. contributed to the conception and design of the manuscript. The first draft of the manuscript was written by S.L. and M.H., and all authors commented on previous versions of the manuscript. The figures in the manuscript were drawn by S.L. and reviewed by M.H. All authors read and approved the final manuscript.
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Liu, S., He, M., Jiang, J. et al. Triggers for the onset and recurrence of psoriasis: a review and update. Cell Commun Signal 22, 108 (2024). https://doi.org/10.1186/s12964-023-01381-0
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DOI: https://doi.org/10.1186/s12964-023-01381-0