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A transmissible ?? intraepithelial lymphocyte hyperproliferative phenotype is associated with the intestinal microbiota and confers protection against acute infection

Jia, L;Wu, G;Alonso, S;Zhao, C;Lemenze, A;Lam, YY;Zhao, L;Edelblum, KL;

Intraepithelial lymphocytes expressing the ?? T cell receptor (?? IELs) serve as a first line of defense against luminal microbes. Although the presence of an intact microbiota is dispensable for ?? IEL development, several microbial factors contribute to the maintenance of this sentinel population. However, whether specific commensals influence population of the ?? IEL compartment under homeostatic conditions has yet to be determined. We identified a novel ?? IEL hyperproliferative phenotype that arises early in life and is characterized by expansion of multiple V? subsets. Horizontal transfer of this hyperproliferative phenotype to mice harboring a phenotypically normal ?? IEL compartment was prevented following antibiotic treatment, thus demonstrating that the microbiota is both necessary and sufficient for the observed increase in ?? IELs. Further, we identified two guilds of small intestinal or fecal bacteria represented by 12 amplicon sequence variants (ASV) that are strongly associated with ?? IEL expansion. Using intravital microscopy, we find that hyperproliferative ?? IELs also exhibit increased migratory behavior leading to enhanced protection against bacterial infection. These findings reveal that transfer of a specific group of commensals can regulate ?? IEL homeostasis and immune surveillance, which may provide a novel means to reinforce the epithelial barrier.