IL‐23 in the Pathogenesis of Rheumatoid Arthritis

Abstract

Interleukin‐23 (IL‐23) is a heterodimeric cytokine belonging to the IL‐6/IL‐12 family that plays a key role in several of autoimmune and inflammatory disorders. This family contains the 34 type I cytokine receptor chains and 27 ligands, which share structural and functional similarities, but on the other hand they display distinct roles in shaping Th cells responses. IL‐12 family cytokines have not only proinflammatory effects but they also promote inflammatory responses. IL‐23 is composed of the p40 subunit in common with IL‐12, and with a unique p19 subunit. IL‐23 binding to an IL‐23 receptor expressed on dendritic cells, macrophages and monocytes triggers the activation of Jak2 and Tyk2, which in turn phosphorylates STAT1, STAT3, STAT4 and STAT5 as well as induce formation of STAT3‐STAT4 heterodimers. IL‐23 is one of the essential factors required for the survival and/or expansion of Th17 cells, which produce IL‐17, IL‐17F, IL‐6 and TNF‐α. Th17 cells stimulated by the IL‐23 promote osteoclastogenesis through production of IL‐17, which induce receptor activator of NF‐kappa B ligand on mesenchymal cells. The IL‐23‐IL‐17 axis includes Th17 cells and plays a key role in the development of autoimmune arthritis.

Role of interleukin-23 as a biomarker in rheumatoid arthritis patients and its correlation with disease activity

“…In keeping with this, IL-17A + and IL-23 + cells co-localize in synovial membranes. So in RA, IL-23 is an important determinant of the production of IL-17A, a cytokine of consequence in inflammation and bone destruction [10].…”

Tolerogenic dendritic cells and rheumatoid arthritis: current status and perspectives

“…Notably, Th17 produces inflammatory cytokines such as IL-17 and is a subset of osteoclastogenic Th cells, which was demonstrated to induce tissue destruction in RA [44][45][46]. IL-23 is essential for the expansion of Th17 cells, and IL-23 receptor is expressed on DCs [47]. Moreover, DCs that are tolerogenic demonstrated reduction in IL-23, which gives rise to lower number of Th17 [48].…”

Decoy receptor 3 regulates the expression of various genes in rheumatoid arthritis synovial fibroblasts

“…IL-12 induces Th1 immune responses, and is thus linked with autoimmune diseases (40), while IL-23 is linked with autoimmune diseases via Th17 immune responses (41). IL-12 (42) and IL-23 (43,44) have also been reported to be involved in the pathogenesis of RA.…”