The intestinal immune system must be tolerant towards commensal microorganisms and food while allowing for the induction of inflammatory responses against pathogens. The mechanisms governing this tolerance are not clearly understood, but loss of this balance can result in commensal- or food-mediated inflammation, leading to intestinal damage. The intestine contains many cell types that can initiate and regulate immune responses, and it is unclear what role each plays in maintaining homeostasis. Two main populations of mononuclear phagocytes reside within the intestine. One is defined by expression of the integrin CD103, and has been described as a migratory dendritic cell (DC). The other expresses the chemokine receptor CX3CR1 and has been compared to tissue resident macrophages. In contrast to previous reports, we recently demonstrated that CX3CR1+ cells migrate from the intestine to the mesenteric lymph node, suggesting that they can behave as DCs. We have generated novel mouse strains allowing depletion of each cell population so that their functions can be studied in vivo. We have found that CX3CR1 and not CD103+ cells are critical for the induction and maintenance of tolerogenic immune responses. We have further demonstrated that antigen presentation by CX3CR1+ cells is critical to prime tolerogenic T cells to intestinal antigens in vivo. This supports our hypothesis that CX3CR1+ cells are DCs that regulate induction of tolerogenic immune responses in vivo.
- Copyright © 2013 by The American Association of Immunologists, Inc.