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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4.

Produced in response to a variety of pathogenic organisms, interleukin (IL)-12 and IL-23 are key immunoregulatory cytokines that coordinate innate and adaptive immune responses. These dimeric cytokines share a subunit, designated p40, and bind to a common receptor chain, IL-12R beta 1. The receptor for IL-12 is composed of IL-12R beta 1 and IL-12R beta 2, whereas IL-23 binds to a receptor composed of IL-12R beta 1 and IL-23R. Both cytokines activate the Janus kinases Tyk2 and Jak2, the transcription factor signal transducer and activator of transcription 4 (STAT4), as well as other STATs. A major action of IL-12 is to promote the differentiation of naive CD4+ T cells into T-helper (Th) 1 cells, which produce interferon (IFN)-gamma, and deficiency of IL-12, IL-12R subunits or STAT4 is similar in many respects. In contrast, IL-23 promotes end-stage inflammation. Targeting IL-12, IL-23, and their downstream signaling elements would therefore be logical strategies for the treatment of immune-mediated diseases.[1]


  1. Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Watford, W.T., Hissong, B.D., Bream, J.H., Kanno, Y., Muul, L., O'Shea, J.J. Immunol. Rev. (2004) [Pubmed]
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