Mouse_Gut_Wellcome_Spatial

T regulatory cells (Tregs) are key players in maintaining gut homeostasis by controlling aberrant immune responses towards microbial antigens. Powrie's lab has previously shown that intestinal infection by the pathobiontHelicobacter Hepaticus (H.h) induces tolerance through the expansion of IL-10 producing Tregs. The murine gut tissue contains hundreds of lymphoid aggregates, which include cryptopatches and isolated lymphoid follicles, but their functional contribution to tissue immunity is currently unclear. We aimed to determine the role of these lymphoid aggregates in the development of microbial antigen-reactive Treg responses. To identify which signals in the lamina propria may drive IL-10 production in response to H.h, we performed niche-seq of lamina propria and lymphoid aggregates and found unique antigen presenting cell subsets at the two sites. Our map of receptor/ligand interactions found on distinct Treg and myeloid cell subsets in different intestinal niches reveals a previously unrecognised spatial mechanism of tolerance at barrier sites.