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|
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.
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.
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