Substantial evidence indicates that the interactions between the commensal microbiota and the immune system of the intestinal tissues of the host may set the stage for development of inflammatory bowel diseases (IBD) in a genetically susceptible host. However, the mechanisms by which immune cells activated by microbial signal can lead to intestinal inflammation are poorly defined.

Among the numerous immune cells that are involved in the pathogenesis of IBD, invariant natural killer T (iNKT) cells are increasingly recognized to play an important role. iNKT cells recognize self- and microbial-lipid antigens presented exclusively by CD1d, a molecule expressed on various antigen presenting cells. Recent evidence shows that CD1d and iNKT cells are involved in both regulating and promoting colonic inflammation. These results suggest the existence of different CD1d bearing cells influencing colonic iNKT cell responses to inflammation. Intestinal Mononuclear Phagocytes (MP) represent macrophages and dendritic cells that are located in lamina propria in humans and mice. Distinct subsets of MP exist that are capable of promoting the induction but also forcing the suppression of mucosal inflammation through their ability to influence T cell response. This led us to investigate the role of different colonic MP subsets in iNKT cell responses.

Using a novel mouse model, which allows for deletion of CD1d in specific populations, we found the existence of MPs with CD1d dependent anti-inflammatory functions in murine colitis. We identified 8 subsets of MPs expressing CD1d in colonic lamina propria and analyzed their capacity to activate iNKT cells. Preliminary results suggest that a specific subset of macrophages expressing the highest level of CD1d among MPs in the lamina propria is a central regulator of iNKT cell responses in colitis.