Fig. 2

The role of IL-33 in inflammation. After allergen exposure and parasite infection, IL-33 is released and activates ST2⁺ mast cells, basophils, eosinophils, ILC2s and Th2 cells to produce type 2 cytokines (IL-4, IL-5, IL-9, IL-13), chemokines (CXCL8, CCL2) promoting the classical type 2 immune response. Additionally, ST2⁺ Treg, CD8⁺ T cells and macrophages are also activated by IL-33 to produce TNF-α and IFN-γ to mediate type I immune responses. In some cases, Increased levels of IL-33 induces ILCs to produce IL-4, which further boosted the mast cell response. And IL-33-stimulated IL-2 production by mast cells or dendritic cells can promote an increase in the number of Treg cells. Moreover, IL-33 acts synergistically with endogenous IL-13 signaling to induce polarization of quiescent TGF-β-producing macrophages to CCL24- and CCL17-producing AAMs, leading to inflammation in the lung. However, in the later stages of inflammation, AAMs can promote resolution of inflammation and tissue repair. And IL-33 induces Treg cells to express amphiregulin (AREG) and thus supports stem cell proliferation and differentiation for tissue repair