E. coli-activated cellular circuit restrains intestinal inflammatory microbiota-specific T cells and protects against colitis

Balance between microbiota-specific effector and regulatory T (Treg) cells is required to promote intestinal health and limit disease pathology. The pathways regulating T cell equilibrium during inflammation and the role of individual microbiota members in these outcomes are still being established. Here, we demonstrate that colonization with a single adherent-invasive Escherichia coli strain restrains pathogenic microbiota-directed T helper type 1 (Th1) cells. This results in a higher proportion of colon Treg cells, specifically tolerogenic microbiota-specific RORγt⁺FoxP3⁺ Treg cells, during intestinal inflammation. This anti-inflammatory shift limits pathology in mouse colitis models. This process requires interleukin-10 production by colon CX₃CR1⁺ antigen-presenting cells to suppress microbiota-specific Th1 cells. This work suggests a mechanism for local circuits that control intestinal T cells to limit microbiota-directed pathology.