Fig. 1

The structure of IL-33 and the regulation of IL-33-ST2 pathway. a The full-length IL-33 (IL-33_FL) is a protein with 270 amino acids. It has the N-terminal nuclear structural domain and the C-terminal IL-1-like cytokine structural domain, with a central dispersed protease sensor region which contains the main site of cleavage of inflammatory proteases. b After epithelial cell exposure to allergens, stress and tissue damage, IL-33_FL will be quickly released from the nucleus and active the ST2 + cells such as ILC2s. In this process, IL-33_FL can be cleaved into shorter mature forms by inflammatory proteases such as neutrophils cathepsin G and mast cells chymase. c IL-33 forms a complex with ST2 and IL-1 receptor accessory protein (IL-1RAcP) leading to the dimerization of the TIR domain. Subsequently, myeloid differentiation primary response protein 88 (MYD88), IL-1R-associated kinase 1 (IRAK1), IRAK4, and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) are recruited. These events further activate nuclear factor-κB (NF-κB) and mitogen-activated protein kinases such as JNK, ERK and p38 which lead to NF-κB and AP-1 pathways respectively. Ultimately pro-inflammatory cytokines begin to be expressed