Group 3 Innate Lymphoid Cells Inhibit T-Cell-Mediated Intestinal Inflammation through Aryl Hydrocarbon Receptor Signaling and Regulation of Microflora

• Ahr-deficient mice have enhanced gut Th17 cells as a result of an expansion of SFB
• IL-22 is important for the control of commensal SFB in the gut
• ILCs play a regulatory role in controlling Th17 cell responses via commensal flora
• Innate expression of Ahr limits T-cell-mediated intestinal inflammation

SummaryAryl hydrocarbon receptor (Ahr) is crucial for the maintenance and function of group 3 innate lymphoid cells (ILCs), which are important in gut immunity. Because Ahr promotes T helper 17 (Th17) cell differentiation in vitro, it is reasonable to expect that Ahr would enhance Th17 cells in vivo. Instead, we show that Ahr deficiency caused increased intestinal Th17 cells, raising the possibility that group 3 ILCs could negatively regulate Th17 cells. Reduced innate interleukin-22 (IL-22) in Ahr-deficient mice allowed expansion of commensal segmented filamentous bacteria (SFB), known to promote Th17 cells. Compared to Rorc+/+Ahr−/− mice, Rorcgfp/+Ahr−/− mice had further reduced group 3 ILCs and were prone to spontaneous colitis with increased SFB and Th17 cells. Innate expression of Ahr played a protective role in T-cell-mediated experimental colitis by suppressing pathogenic Th17 cells. Our data reveal an intricate balance between ILCs and Th17 cells regulated by Ahr and commensal flora.