The cytokines interleukin 27 and interferon-γ promote distinct Treg cell populations required to limit infection-induced pathology.
Authors:
Hall, Aisling O'Hara Beiting, Daniel P Tato, Cristina John, Beena Oldenhove, Guillaume Lombana, Claudia Gonzalez Pritchard, Gretchen Harms Silver, Jonathan S Bouladoux, Nicolas Stumhofer, Jason S Harris, Tajie H Grainger, John Wojno, Elia D Tait Wagage, Sagie Roos, David S Scott, Philip Turka, Laurence A Cherry, Sara Reiner, Steven L Cua, Daniel Belkaid, Yasmine Elloso, M Merle Hunter, Christopher A
Interferon-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.