Influence Of Anti-CTLA-4Monoclonal Antibodies On Murine Colitis Through Changing Th17-treg Profile

Objective To investigate the influence of anti-mouse CTLA-4monoclonal antibodies (anti-CTLA-4) on the immune response of murine model of ulcerative colitis in terms of the change of Thl7and Treg.Methods3%Dextran sulfate sodium induced colitis was made in the male C57BL/6mice. Disease activity index, macroscopical and histological scores, and myeloperoxidase activity were detected and the relatively expression of the cytokine involved in Thl7and Treg was examined. Moreover, the murine colitis models were randomly assigned to two groups:the intervention group was injected intraperitoneally with200ug of anti-CTLA-4mab each day for7days while the control group was injected200ug of the isotype IgG in the same way and time. Disease activity index, macroscopical and histological scores, and myeloperoxidase activity were evaluated and the mRNA or proteic expression of Thl7-Treg related cytokine was discovered. Immunohistochemical method was used to explore IL-17A and STAT-3in colonic tissue.Results The acute colitis model was built successfully with significantly increased disease activity index, macroscopical and histological scores, and myeloperoxidase activity. The relative expression level of TNF-a, IL-17A, RORyt, Foxp3and STAT-3increased while TGF-J3decreased (p<0.05, respectively). Mice treated with anti-CTLA-4showed amelioration of colitis with lower disease activity index, myeloperoxidase activity and histological scores of colonic tissue as well as less shortened length of colon (p＜0.05, respectively). Besides, Thl7cells decreased (p<0.05) and Treg cells increased in mesenteric lymph node (p<0.05). Moreover, the relative expression level of TNF-a, IL-17A, and RORyt reduced wihle Foxp3, TGF-β and STAT-3elevated (p<0.05, respectively). Protein expression of JAK-2, RORyt and IL-17A was reduced but level of STAT-3, phosphorylated STAT-3and Foxp3was up-regulated (P<0.05, respectively).Conclusion Blocking CTLA-4function with anti-CTLA-4alleviated DSS-induced colitis in mice through changing the immune responses of Thl7-Treg profile, which suggests anti-CTLA-4as a potential therapeutic method for the therapy of ulcerative colitis.