The mucosal immune system mediates contact between the host and the trillions of microbes that symbiotically colonize the gastrointestinal tract. Failure to tolerate the antigens within this “extended self” can result in inflammatory bowel disease (IBD). Within the adaptive immune system, the most significant cells modulating this interaction are Foxp3+ regulatory T (Treg) cells. Treg cells can be divided into 2 primary subsets: “natural” Treg cells and “adaptive” or “induced” Treg. Recent research suggests that these subsets serve to play both independent and synergistic roles in mucosal tolerance. Studies from both mouse models and human patients suggest that defects in Treg cells can play distinct causative roles in IBD. Numerous genetic, microbial, nutritional, and environmental factors that associate with IBD may also affect Treg cells. In this review, we summarize the development and function of Treg cells and how their regulatory mechanisms may fail, leading to a loss of mucosal tolerance. We discuss both animal models and studies of patients with IBD suggesting Treg cell involvement in IBD and consider how Treg cells may be used in future therapies.
Article first published online 6 May 2013
Section of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
Reprints: Calvin B. Williams, MD, PhD, Section of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226 (e-mail: email@example.com).
The authors have no conflicts of interest to disclose.
Supported by the National Institutes of Health (NIH) F32 AI092977 (C.G.M.), a Senior Research Award #2858 from the Crohn's and Colitis Foundation of America (C.B.W.), NIH R01 AI073731 and R01 AI085090 (C.B.W.), and the D.B. and Marjorie Reinhart Family Foundation (C.B.W.).
Received November 01, 2012
Accepted November 6, 2012