Interleukin-23 (IL-23) is a heterodimeric cytokine composed of an IL12B (IL-12p40) subunit (that is shared with IL12) and the IL23A (IL-23p19) subunit. A functional receptor for IL-23 (the IL-23 receptor) has been identified and is composed of IL-12R β1 and IL-23R.
Crystal structure of IL-12B
|Alt. symbols||CLMF2, NKSF2, p40|
|Locus||Chr. 5 q31.1-33.1|
|interleukin 23, alpha subunit p19|
|Locus||Chr. 12 q13.13|
IL-23 is a proinflammatory cytokine. IL-23 has been shown to be a key cytokine for Th17 maintenance and expansion. Th17 are polarised by IL-6 and TGF-β which activate Th17 transcription factor RORγt. IL-23 stabilises RORγt and thus enables Th17 to properly function and release their effector cytokines such as IL-17, IL-21, IL-22 and GM-CSF which mediate protection against extracellular parasites (fungi and bacteria) and participate in barrier immunity.  Similar effects as IL-23 has on Th17 cells were described on type 3 innate lymphoid cells which actively secrete Th17 cytokines upon IL-23 stimulation.  NK cells express IL-23 receptor too. They respond with increased IFN-γ secretion and enhanced antibody-dependent cellular cytotoxicity. IL-23 also induces proliferation of CD4 memory T cells (not naïve cells).  Along with mentioned proinflammatory effects IL-23 promotes angiogenesis. 
IL-23 is mainly secreted by activated dendritic cells, macrophages or monocytes. Secretion is stimulated by an antigen stimulus recognised by a pattern recognition receptor.  IL-23 imbalance and increase is associated with autoimmune and cancerous diseases. It is thus a target for therapeutic research. 
Prior to the discovery of IL-23, IL-12 had been proposed to represent a key mediator of inflammation in mouse models of inflammation. However, many studies aimed at assessing the role of IL-12 had blocked the activity of IL-12p40, and were therefore not as specific as thought. Studies which blocked the function of IL-12p35 did not produce the same results as those targeting IL-12p40 as would have been expected if both subunits formed part of IL-12 only.
The discovery of an additional potential binding partner for IL-12p40 led to a reassessment of this role for IL-12. Seminal studies in experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis, showed that IL-23 was responsible for the inflammation observed, not IL-12 as previously thought. Subsequently, IL-23 was shown to facilitate development of inflammation in numerous other models of immune pathology where IL-12 had previously been implicated including models of arthritis, intestinal inflammation, and psoriasis. Ustekinumab, a monoclonal antibody directed against this cytokine, is used clinically to treat certain autoimmune conditions.
IL-23 heterodimer binds the receptor complex - p19 subunit binds IL-23R while p40 subunit binds IL-12RB1 which leads to recruitment of Janus kinase 2 and Tyrosine kinase 2 kinases. Janus kinase 2 and Tyrosine kinase 2 transduce the signal and phosphorylate STAT3 and STAT4. STATs dimerise and activate transcription of target genes in nucleus. STAT3 is responsible for key Th17 development attributes like RORγt expression or transcription of Th17 cytokines.
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