Microbiota dampen type 2 immunity by epigenetically restricting tuft cell differentiation

Abstract Type 2 immune responses at mucosal surfaces are both required to expel helminthic parasites and central allergic disease pathogenesis. Tuft cells regulators of type immunity that instruct downstream innate lymphoid (ILC2s). Although the microbiota known shape responses, impact commensal microbes on regulation tuft cell-dependent remains poorly understood. Here, we find butyrate-producing bacteria suppress in intestine. Butyrate suppression microbiota-sensitive epigenetic modifying enzyme histone deacetylase 3 (HDAC3), suggesting HDAC3 may promote defense. Consistent with this, epithelial-intrinsic actively stimulated cell was initiate cell-ILC2 feed-forward response Nippostrongylus brasiliensis infection, promoted expulsion this parasite. Furthermore, butyrate epigenetically restricted stem differentiation into cells, inhibition adult mice human intestinal organoids sufficient block differentiation. Collectively, these data reveal a pathway dampens mediated immunity, highlight new level through which can calibrate inflammation. This research is supported by National Institutes Health (DK114123, DK116868 T.A., F32AI147591 E.M.E.), Kenneth Rainin Foundation award T.A. holds an Investigator Pathogenesis Infectious Disease Award from Burroughs Wellcome Fund. project part PHS grant P30 DK078392 CCHMC Trustee Procter Scholar’s Program.