Critical Role for the Microbiota in Regulation of Intestinal T Cells

The paper published by Kim et al. discusses the crucial role of intestinal microbiota for the induction of the mucosal tolerance. Microbiota acts by limiting Th1 and supporting Treg cell responses against luminal antigens. Kim et al. demonstrated that microbial epithelial attachment is required to activate the anti-inflammatory T cell responses through IL-10 production by CX3CR1+ mononuclear phagocytes.

Kim et al. identified a regulatory loop whereby, in the presence of the normal microbiota, intestinal antigen-presenting cells (APCs) expressing the chemokine receptor CX3CR1 reduced expansion of intestinal microbe-specific T helper 1 (Th1) cells and promoted generation of regulatory T cells responsive to food antigens and the microbiota itself. They demonstrate that disruption of the microbiota resulted in CX3CR1+ APC dependent inflammatory Th1 cell responses with increased pathology after pathogen infection.

Colonization with microbes that can adhere to the epithelium is able to compensate for intestinal
microbiota loss, indicating that although microbial interactions with the epithelium can be pathogenic, they can also activate homeostatic regulatory mechanisms. This team’s results identify a cellular mechanism by which the microbiota limits intestinal inflammation and promotes tissue homeostasis.