Fig. 5

Other triggers that have been implicated in the development of psoriasis (by Figdraw, www.figdraw.com). Smoking behaviors may trigger psoriasis by activating inflammatory, oxidative, and genetic mechanisms that are mediated by free radicals and nicotine. Skin injury results in damage to KCs and subsequent release of dsRNA, ssRNA, DNA, and LL-37. pDCs mainly produce IFN-α by activating TLR7 or TLR9 with presence of DNA/ssRNA–LL-37 complexes, while KCs exposed to LL-37 produce IFN-β by recognizing CpG/genomic DNA or ssRNA–LL-37 complex via TLR9 and TLR3, respectively. Mechanical stretch induces the production of proinflammatory cytokines, AMPs, and chemokines by KCs in psoriasis. Medications, such as lithium, β-blockers, IFN, IMQ, and antimalarial agents, may trigger the proliferation of KCs. Sleep loss promotes the activities of kallikrein-5 and kallikrein-7 in the psoriatic skin, leading to epidermal barrier destruction. In addition, sleep loss also induces stress, which subsequently triggers psoriasis through the HPA axis, peripheral nervous system, and immune pathways. Upon stress, CRH activates MCs to release various cytokines and chemokines, such as IL-1, IL-6, IL-31, TNF, and CXCL-8. Stress stimulates the release of neuropeptides, including NT, SP, NGF, and PACAP from cutaneous peripheral nerve endings, thereby promoting the onset of neurogenic inflammation with MC activation. CRH also facilitates the penetration of the inflammatory cells in the psoriasis plaques by enhancing angiogenesis and increasing vascular permeability