Critical Roles of IL-33/ST2 Pathway in Neurological Disorders

Figure 2

Releases and signalling of IL-33. Full length of IL-33 is predominantly expressed by stromal cells, endothelial and epithelial cells, macrophages, and fibroblasts. In necrosis, IL-33 is released and binds to ST2L/IL1-RAcP heterodimer receptor, which induces signalling via TIR domain of ST2L/IL1-RAcP and recruits MyD88 and followed by IRAK1/4 and TRAF6. TRAF6 further induces either MAPK which in turns activating P38, ERK and JNK, and/or IKK pathway which activate NF-κB. Both pathways lead to the recruitment of transcription factors and proinflammatory cytokines, which consequently drives the regulatory transcription factors of Th2 cytokines and chemokines. Alternatively, binding of IL-33 to sST2 neutralises the proinflammatory effect of IL-33 as well as with SIGIRR which negatively regulates ST2L signalling pathway. In apoptosis, IL-33 is cleaved and deactivated by caspase-3/7.