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

T helper 17 (T_H17) 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 (T_FH) 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 T_FH-dominated response with only rare antigen-specific T_H17 cells (<8%) in the PP. A clonotypic analysis provided little support that clonotypes were shared between T_FH and T_H17 cells, arguing against T_H17 plasticity as a major contributor to T_FH differentiation. Two mouse models of T_H17 deficiency confirmed that gut IgA responses to oral immunization do not require T_H17 cells, with CD4^CreRorc^fl/fl mice exhibiting normal germinal centers in PP and unperturbed total IgA production in the intestine.