Nils Lycke

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