Like many cytokines, IL-27 has pleiotropic properties that can limit or enhance ongoing immune responses depending on context. Thus, under certain circumstances, IL-27 can promote TH1 differentiation and has been linked to the activation of CD8(+) T cells and enhanced humoral responses. However, IL-27 also has potent inhibitory properties and mice that lack IL-27 mediated signaling develop exaggerated inflammatory responses in the context of infection or autoimmunity. This chapter reviews in depth the biology of IL-27, including the initial discovery, characterization, and signaling mediated by IL-27 as well as more recent insights into the molecular and cellular basis for its pleiotropic effects. Many of these advances are relevant to human diseases and highlight the potential of therapies that harness the regulatory properties of IL-27.
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