Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T _H17 cells in the intestine

T _H17 cells are a lineage of CD4+ T cells that are critical for host defense and autoimmunity by expressing the cytokines IL-17A, IL-17F, and IL-22. A feature of T _H17 cells at steady state is their ubiquitous presence in the lamina propria of the small intestine. The induction of these steady-state intestinal T _H17 (sT _H17) cells is dependent on the presence of the microbiota. However, the signaling pathway linking the microbiota to the development of intestinal sT _H17 cells remains unclear. In this study, we show that IL-1β, but not IL-6, is induced by the presence of the microbiota in intestinal macrophages and is required for the induction of sT _H17 cells. In the absence of IL-1β-IL-1R or MyD88 signaling, there is a selective reduction in the frequency of intestinal sT _H17 cells and impaired production of IL-17 and IL-22. Myeloid differentiation factor 88-deficient (MyD88 ^-/-) and germ-free (GF) mice, but not IL-1R ^-/- mice, exhibit impairment in IL-1β induction. Microbiota-induced IL-1β acts directly on IL-1R-expressing T cells to drive the generation of sT _H17 cells. Furthermore, administration of IL-1β into GF mice induces the development of retinoic acid receptor-related orphan receptor γt-expressing sT _H17 cells in the small intestine, but not in the spleen. Thus, commensal-induced IL-1β production is a critical step for sT _H17 differentiation in the intestine, which may have therapeutic implications for T _H17-mediated pathologies.