In the gut, there are tremendous antigens existed such as food proteins, commensal bacteria and even self-antigens. For this reason, maintenance of intestinal tolerance is important to regulate excessive inflammations. Recently, Foxp3+ Tregs are required to maintain intestinal tolerance. However, their phenotypes and functions in immune regulation are heterogeneous, thus it is required to find which subpopulations of Tregs in the gut suppress inflammatory cells effectively to prevent inflammatory diseases. Here we found that majority of the Tregs in the small intestinal lamina propria highly express CD103 molecule on their surface compared to Tregs in other tissues such as thymus, spleen, mesenteric lymph nodes and colon. We next investigated which antigen presenting cells from small intestinal lamina propria can induce CD103+ Tregs in vitro. We found that intestinal CX3CR1+ macrophages, which produce immunoregulatory cytokine IL-10 highly, induce CD103+ Tregs more efficiently, but not dendritic cells. These CD103+ Tregs had effect on reducing occurrence of diarrhea in food allergy model. Further, intestinal CX3CR1+ macrophages induced helios+ Tregs which have been recently suggested to be stable Tregs, under inflammatory stimulations. These findings suggest that CD103+ Tregs induced by intestinal CX3CR1+ macrophages raise the possibility of improvement in therapeutic potential of Tregs for inflammatory diseases such as graft versus host diseases and autoimmune diseases.
- Copyright © 2013 by The American Association of Immunologists, Inc.