IL-23, which is composed of p19 and p40 subunits, is a proinflammatory cytokine that contributes to the formation and maintenance of Th17 cells in inflammatory autoimmune diseases.
Interleukin-23 (IL-23)/IL-23 receptor (IL-23R) is essential for Th17 cell-mediated immune response, involved in autoimmune diseases and cancer pathogenesis.
Therefore, AS2762900-00 represents a potent novel IL-23-IL-17 pathway inhibitor with the potential to be developed into a new therapy for the treatment of autoimmune diseases.
Since the IL-23/IL-17 pathway is known to associate with other autoimmune disease, including rheumatoid arthritis and systemic sclerosis, we hypothesised that IL23R could be a shared susceptibility gene.
IL-23 specifically contributes to the inflammatory process of multiple chronic inflammatory autoimmune disorders, including psoriasis, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis.
IL-23 binds IL-23R on the surface of target cells and transmits signals through Janus kinase 2/signal transducer and activator of transcription channels, participating in the occurrence of chronic inflammatory diseases and autoimmune diseases.
The selective requirement of JunB for IL-23-dependent T<sub>H</sub>17 pathogenicity suggests that the JunB-dependent pathway may be a therapeutic target for autoimmune diseases.
Interleukin-23 (IL-23) is an important proinflammatory cytokine well known for its role in neutrophil recruitment in various infectious and autoimmune diseases.
Allelic variants of p19 subunit of IL-23 (IL23A) and IL-23 receptor (IL23R) genes and increased IL-23 serum concentrations were associated with autoimmune diseases.
Unveiling of an alternative pathway in the IL-23-regulated resistance might provide a novel strategy against infectious pathogens without side effects of autoimmunity.
Nevertheless, biological drugs that target the IL-23-IL-17 pathway are highly effective in treating human psoriasis and are showing promise in the treatment of relapsing remitting MS and other T-cell mediated autoimmune diseases.
IL-17 is a crucial effector cytokine, whose production is specifically triggered by IL-23, and it has been shown to be an essential inflammatory mediator in other autoimmune diseases and inflammatory conditions.
These data reveal that the lupus-associated Ro52 protein is an important negative regulator of proinflammatory cytokine production, and they provide a mechanism by which a defective Ro52 function can lead to tissue inflammation and systemic autoimmunity through the IL-23-Th17 pathway.
The interleukin (IL)-17/IL-23 axis that emerged as the new paradigm has compelled us to critically re-examine the cytokine-driven immune events in the pathogenesis and treatment of autoimmunity.
Mice lacking IL-23 (p19-/-) do not develop experimental autoimmune encephalomyelitis (EAE) or collagen-induced arthritis (CIA), while knockout mice for the Th1 cytokine IL-12 (p35-/-) strongly develop both autoimmune diseases.
Because microglia produce IL-1beta and IL-23, these cytokines may act in an autocrine manner to induce IL-17 expression in microglia, and thereby contribute to autoimmune diseases, such as MS, in the central nervous system.
Previous studies have explicitly shown that psoriasis is an autoimmune disease that is predominantly mediated by T helper 17 (Th17) cells, which express high levels of interleukin-17 (IL-17) in response to interleukin-23 (IL-23).