期刊
IMMUNOLOGICAL REVIEWS
卷 202, 期 -, 页码 139-156出版社
WILEY
DOI: 10.1111/j.0105-2896.2004.00211.x
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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-12Rbeta1. The receptor for IL-12 is composed of IL-12Rbeta1 and IL-12Rbeta2, whereas IL-23 binds to a receptor composed of IL-12Rbeta1 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.
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