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

Wendy T. Watford, Bruce D. Hissong, Jay H. Bream, Yuka Kanno, Linda Muul, John J. O'Shea

Research output: Contribution to journalReview articlepeer-review

410 Scopus citations


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-12Rβ1. The receptor for IL-12 is composed of IL-12Rβ1 and IL-12Rβ2, whereas IL-23 binds to a receptor composed of IL-12Rβ1 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 naïve CD4+ T cells into T-helper (Th) 1 cells, which produce interferon (IFN)-γ, 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.

Original languageEnglish (US)
Pages (from-to)139-156
Number of pages18
JournalImmunological reviews
StatePublished - Dec 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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