Interleukin 23 (IL-23) is a heterodimeric cytokine composed of two disulfide-linked subunits, a p19 subunit that is unique to IL-23, and a p40 subunit that is shared with IL-12. The p19 subunit has homology to the p35 subunit of IL-12, as well as to other single chain cytokines such as IL-6 and IL-11. The p40 subunit is homologous to the extracellular domains of the hematopoietic cytokine receptors. Although p19 is expressed by activated macrophages, dendritic cells, T cells, and endothelial cells, only activated macrophages and dendritic cells express p40 concurrently to produce IL-23. IL-23 has biological activities that are similar to, but distinct from IL-12. Both IL-12 and IL-23 induce proliferation and IFN-gamma production by human T cells. While IL-12 acts on both naive and memory human T cells, the effects of IL-23 is restricted to memory T cells.
Associates with IL12B to form the pro-inflammatory cytokine IL-23 that plays different roles in innate and adaptive immunity. Released by antigen-presenting cells such as dendritic cells or macrophages, binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R to activate JAK2 and TYK2 which then phosphorylate the receptor to form a docking site leading to the phosphorylation of STAT3 and STAT4. This process leads to activation of several pathways including p38 MAPK or NF-kappa-B and promotes the production of pro-inflammatory cytokines such as interleukin-17A/IL17A. In turn, participates in the early and effective intracellular bacterial clearance. Promotes the expansion and survival of T-helper 17 cells, a CD4-positive helper T-cell subset that produces IL-17, as well as other IL-17-producing cells.
IL-23 , which is mainly secreted by antigen-presenting cells , is a member of the IL-12 family , which includes IL-12 , IL-27 , and IL-35. IL-23 is a heterodimeric cytokine , comprised of a unique p19 subunit and p4 subunit , the latter of which is shared with IL-12. The receptor for IL-23 consists of IL-23R and IL-12Rβ1 , the latter of which is also characteristic of IL-12. IL-23 is essential for Th17 differentiation , expansion , and survival by binding to its receptor , thereby activating the signaling pathway. Many studies revealed that the IL-23/Th17 pathway is implicated in the pathophysiology of various autoimmune diseases , such as autoimmune arthritis , primary biliary cirrhosis , and inflammatory bowel disease.
Interleukin 23 receptor (IL23R) is a type I cytokine receptor for IL23. IL23 receptor complex is comprised of two subunits; the IL12Rβ1 subunit; which is shared with several cytokines; and a subunit that is unique to IL-23. IL23; after binding to IL23R; activates memory T cells and mediates pro-inflammatory activities in part by the production of IL17 through activation of TH17 lymphocytes. IL23R is expressed on T cells; NK cells; dendritic cells; and macrophages. In fact; polymorphisms of the IL23R gene were reported to be associated with susceptibility to inflammatory diseases and autoimmune diseases such as psoriasis; multiple sclerosis; Graves's ophtalmopathy and inflammatory bowel diseases. The IL23R is known to be critically involved in the carcinogenesis of different malignant tumor.
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