Breaking down oral barriers (1)

Introduction to IL-23

Interleukin-23 (IL-23) is a member of the IL-12 cytokine family and a heterodimeric cytokine composed of two subunits, p19 and p40. Its receptor IL-23R is composed of two subunits, IL-23R α and IL-12R β 1. Among them, p19 specifically binds to IL-23R α, while p40 binds to IL-12R β subunits on IL-23 or IL-12 (as shown in the figure below). When IL-23 binds to IL-23R, it triggers downstream phosphorylation of JAK2 and TYK2, activating signaling pathways and leading to phosphorylation of STAT proteins, ultimately promoting the expression of cytokines such as IL-17A, IL-17F, IL-22, and IFN - γ. The IL-23 signaling pathway involves phosphorylation of multiple STAT proteins, but its biological activity is mainly mediated by STAT3

IL-23 released by myeloid cells after tissue injury amplifies the inflammatory response by driving the Th17/IL-17 signaling axis, which has been confirmed as the core pathogenic mechanism of psoriasis (PsO) and psoriatic arthritis (PsA). Targeted IL-23p19 therapy can significantly improve skin and joint symptoms and help restore immune homeostasis. Meanwhile, IL-23 is highly expressed in the intestinal mucosal tissues of patients with ulcerative colitis (UC) and Crohn's disease (CD). By activating Th17 cells and other immune cells, it promotes the release of pro-inflammatory cytokines such as IL-17A, IL-17F, and IL-22, further exacerbating intestinal inflammatory responses (such as damaging intestinal epithelial cells and disrupting the integrity of the intestinal barrier). Therefore, inflammatory bowel disease (IBD) has also become an important potential indication for targeted IL-23 signaling pathway therapy.