The Cytokines Interleukin 27 and Interferon-γ Promote Distinct Treg Cell Populations Required to Limit Infection-Induced Pathology

SummaryInterferon-γ (IFN-γ) promotes a population of T-bet+ CXCR3+ regulatory T (Treg) cells that limit T helper 1 (Th1) cell-mediated pathology. Our studies demonstrate that interleukin-27 (IL-27) also promoted expression of T-bet and CXCR3 in Treg cells. During infection with Toxoplasma gondii, a similar population emerged that limited T cell responses and was dependent on IFN-γ in the periphery but on IL-27 at mucosal sites. Transfer of Treg cells ameliorated the infection-induced pathology observed in Il27−/− mice, and this was dependent on their ability to produce IL-10. Microarray analysis revealed that Treg cells exposed to either IFN-γ or IL-27 have distinct transcriptional profiles. Thus, IFN-γ and IL-27 have different roles in Treg cell biology and IL-27 is a key cytokine that promotes the development of Treg cells specialized to control Th1 cell-mediated immunity at local sites of inflammation.

► IL-27 promotes Treg cells that express T-bet, CXCR3, and IL-10 ► Treg cells prevent infection-induced immune pathology in Il27−/− mice ► IL-27 and IFN-γ have distinct effects on Treg cell biology at local and peripheral sites