The Functional Roles of IL-33/ST2 Axis in Ocular Diseases

Figure 1

Signaling and roles of IL-33/ST2 in eye diseases. Various factors (infection, allergy, tissue damage, and stressful stimuli, etc.) result in the release of interleukin-33 (IL-33) from the nucleus of endothelial cells, epithelial cells, fibroblasts, and Müller cells. Binding of IL-33 with heterodimer receptor suppression of tumorigenicity 2 (ST2L)/IL-1R accessory protein (IL-1RAcP) induces myeloid differentiation primary response protein 88 (MyD88) recruitment via Toll-interleukin 1 receptor (TIR) domain and downstream activation involving IL-1R-associated kinase 1 (IRAK1), IRAK4, and tumor necrosis factor receptor-associated factor 6 (TRAF6). Subsequently, the p38-activated mitogen-activated protein kinases (MAPK), c-Jun N-terminal kinase (JNK), extracellular regulated protein kinases (ERK), and nuclear factor kappa B (NF-κB) promote the secretion of inflammatory cytokines and chemokines, which in turn exerts pro-/anti-inflammatory effect and tissue repairment. Upregulated IL-33 in different parts of eyeball and ocular adnexa induces diverse immune responses and diseases by targeting various ST2+ cells.