Fig. 1

Signaling pathways of RELMα and RELMβ inducing the inflammation in the lung and colon. RELMα promotes IL-6 expression in macrophages in a HIF-1α-dependent manner. RELMα induces a series of inflammatory cytokines and chemokines such as interleukin IL-1β, -1ra, -16 and -17; CXCL-1, -2, -9, -10, -13; MCP-1; M-CSF; TIMP-1; and TREM-1 in BALF. RELMα induces acetylation of HMGB1 by inhibiting deacetylase Sirt 1, thereby enhancing vascular inflammation. RELMα promotes the release of inflammatory cytokines such as serum IL-1β, IL-6, IL-8, TNF-α, and CRP. M2 macrophage-derived RELMα binding to CD4⁺ T cells can attenuate lung inflammatory response by decreasing the production of Th2 cytokines (IL-4, IL-5, and IL-13) derived from CD4⁺ T cells in a BTK-dependent manner. Lung B cells can produce RELMα to downregulate IL-17A of γδ T cells, thereby limiting emphysema. RELMα exacerbates intestinal inflammation by promoting the IL-23p19/IL-17A immune axis. Eosinophils-derived RELMα promotes BMD macrophage activation by synergizing with LPS to amplify LPS-induced proinflammatory cytokine (IL-6 and TNF-α) secretion and suppresses anti-inflammatory cytokines (IL-10) production. RELMα induces proinflammatory eosinophil-directed cytokines (such as IL-5, CCL11, and CCL5) and IL-17. Goblet cell-derived RELMβ stimulates TNF-α, IL-6, and CCL5 in macrophages, thereby promoting intestinal inflammation. RELMβ-exposed macrophages induce expression of MHC II and secretion of IL-12/23p40, which can increase IFN-γ production by effector Th1 cells recruited to areas of inflammation