Laboratory of Cell Biology, Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
Correspondence: David M. Frucht, Building 29B, Room 3NN22, DMA/CBER/FDA, Bethesda, MD 20892. E-mail: frucht{at}cber.fda.gov
Recent discoveries of interleukin (IL)-23, its receptor, and its signal-transduction pathway add to our understanding of cellular immunity. IL-23 is a heterodimer, comprising IL-12 p40 and the recently cloned IL-23-specific p19 subunit. IL-23 uses many of the same signal-transduction components as IL-12, including IL-12Rß1, Janus kinase 2, Tyk2, signal transducer and activator of transcription (Stat)1, Stat3, Stat4, and Stat5. This may explain the similar actions of IL-12 and IL-23 in promoting cellular immunity by inducing interferon-
production and proliferative responses in target cells. Additionally, both cytokines promote the T helper cell type 1 costimulatory function of antigen-presenting cells. IL-23 does differ from IL-12 in the T cell subsets that it targets. Whereas IL-12 acts on naïve CD4+ T cells, IL-23 preferentially acts on memory CD4+ T cells. This review summarizes recent advances regarding IL-23, providing a functional and mechanistic basis for the unique niche that IL-23 occupies in cellular immunity.
Key Words: IL-23R • IL-12 • IL-12R • Stat4
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