Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells

T regulatory cells that express the transcription factor Foxp3 (Foxp3(+) T-regs) promote tissue homeostasis in several settings. We now report that symbiotic members of the human gut microbiota induce a distinct T-reg population in the mouse colon, which constrains immunoinflammatory responses. This induction-which we find to map to a broad, but specific, array of individual bacterial species-requires the transcription factor Ror gamma, paradoxically, in that Ror gamma is thought to antagonize FoxP3 and to promote T helper 17 (T(H)17) cell differentiation. Ror gamma's transcriptional footprint differs in colonic T-regs and T(H)17 cells and controls important effector molecules. Ror gamma, and the T-regs that express it, contribute substantially to regulating colonic T(H)1/T(H)17 inflammation. Thus, the marked context-specificity of Ror gamma results in very different outcomes even in closely related cell types.