Peyer’s patch T_H17 cells are dispensable for gut IgA responses to oral immunization

T helper 17 (TH17) cells located at the Peyer’s patch (PP) inductive site and at the lamina propria effector site of the intestinal immune system are responsive to both pathogenic and commensal bacteria. Their plasticity to convert into follicular helper T (TFH) cells has been proposed to be central to gut immunoglobulin A (IgA) responses. Here, we used an IL-17A fate reporter mouse and an MHC-II tetramer to analyze antigen-specific CD4+T cell subsets and isolate them for single-cell RNA sequencing after oral immunization with cholera toxin and ovalbumin. We found a TFH-dominated response with only rare antigen-specific TH17 cells (<8%) in the PP. A clonotypic analysis provided little support that clonotypes were shared between TFHand TH17 cells, arguing against TH17 plasticity as a major contributor to TFHdifferentiation. Two mouse models of TH17 deficiency confirmed that gut IgA responses to oral immunization do not require TH17 cells, withCD4CreRorcfl/flmice exhibiting normal germinal centers in PP and unperturbed total IgA production in the intestine.