Analysis of murine and human Treg subsets in inflammatory bowel disease

Previous studies have indicated that regulatory T cells serve essential roles in maintaining intestinal homeostasis, however, the role of different Treg subsets in modulating inflammatory bowel disease has still not been addressed clearly. In the present study, the authors measured the percentage of Foxp3+ IL-10+ TGF-β+ natural Tregs, Foxp3− IL-10+ TGF-β− induced Tregs, CD127− induced Tregs and CD8+ Tregs at different time points in DSS-induced experimental colitis model in murine lamina propria lymphocytes, mesenteric lymph node and peripheral blood. In addition, the authors compared the frequency of four Treg subsets in patients diagnosed of ulcerative colitis at different stages with enrolled healthy controls. The percentage of Foxp3+ IL-10+ TGF-β+ natural Tregs decreased in acute stage of both human and mice was observed, but proliferated significantly during remittent stage. Foxp3− IL-10+ TGF-β− inducible (i) Treg and CD127− iTreg was observed as being significantly decreased percentage in LPL at 4 and 7 days, the frequency of Foxp3− IL-10+ TGF-β− iTreg cells became decreased and CD127− iTreg only slightly increased at the chronic stage following DSS induction. However, the proportion of both Foxp3− IL-10+ TGF-β− iTreg and CD127− iTreg was nearly unchanged in human IBD. Although intestinal inflammation decreased the percentage of CD8+ Tregs, it remained lower in the remittent stage of human IBD. Only enhanced proliferation of lamina propria lymphocytes-derived CD8+ Treg was reported at 7 days in dextran sodium sulfate-induced murine colitis. The results demonstrated that Foxp3+ IL-10+ TGF-β+ natural Tregs may serve an essential role in exhibiting suppressive and protecting from immune-related mucosal injury during chronic stage in inflammatory bowel disease.