CD200:CD200R interactions have been shown to lead to potent immunosuppression, resulting in enhanced allograft survival; reduced collagen-induced arthritis; and increased growth of leukemic, lymphoma cells and breast cancer cells. We have investigated the effect of "knockout"of CD200R, or over-expression of CD200 in transgenic mice (CD200tg), on susceptibility to dextran sodium sulfate (DSS) induced colitis in C57BL/6 female mice. Control animals given DSS developed weight loss (~15%) and diarrhoea over 7 days, before slow recovery. These effects were more pronounced in CD200RKO mice, with ~40% mortality at day 7. In contrast CD200tg mice showed attenuation of all symptoms. Immunohistological analysis and protein expression array confirmed severe inflammation in CD200RKO and controls, with loss of villi, inflitration by macrophages, neutrophils and CD3+ cells, and high expression levels of IL-1β and TNF-α in the intestine. In CD200tg mice intestinal tissue showed enhanced inflitration by Foxp3+Tregs, with increased expression of IL-10. Taken together these data suggest for the first time that CD200:CD200R interactions play a role in regulating inflammatory colitis in mice, which may open new avenues for treatment of inflammatory diseases in man.
- Copyright © 2013 by The American Association of Immunologists, Inc.