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IL-12 Family & Receptor

IL-12 Family & Receptor

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    IL-12 Family & Receptor Background

    The Interleukin-12 (IL-12, IL12) family cytokines, including IL-12, IL-23, IL-27 and IL-35, are key players in the regulation of T cell responses. Interleukin-12 (IL-12, IL12) has long been appreciated to play central role in the generation of TH1 cells. Subsequent studies indicated that IL-23 and IL-27, two cytokines that are closely related to IL-12, also regulate TH1-cell responses. IL-12 is composed of p35 and p40 subunits. IL-23 is composed of the IL-12p40 subunit and the IL-23p19 subunit, which shares homology with IL-12p35. IL-27 is composed of EBI3/IL-27B and p28. IL-35, a novel member of IL-12 family, is composed of the IL-12p35 and EBI3 subunits. IL-35 is secreted by regulatory T cells, and suppresses inflammatory responses of immune cells.

    Function of the IL-12 family members largely depend on IL-12 family receptors. IL-12 and IL-23 bind to IL-12Rβ1/IL-12Rβ2 and IL-12Rβ1/IL-23R, respectively. IL-12Rβ2 is considered to play a key role in IL-12 function. Upon binding, IL-12Rβ2 becomes tyrosine phosphorylated and provides binding sites for kinases, Tyk2 and Jak2. These are important in activating the JAK-STAT pathway. In regulating the activity of B and T lymphocytes, the effects of IL-27 are eliciting by its interaction with a specific cell surface receptor complex composed of two proteins known as IL-27R and gp130.

    IL-12 Family & Receptor References

      1. Hunter CA. (2005) New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat Rev Immunol. 5(7):521-31.
      2. Del Vecchio M, et al. (2007) Interleukin-12: biological properties and clinical application. Clin Cancer Res. 13(16):4677-85.
      3. Gee K, et al. (2009) The IL-12 family of cytokines in infection, inflammation and autoimmune disorders. Inflamm Allergy Drug Targets. 8(1):40-52.