Anti-mouse CD52 Treatment Ameliorates Colitis through Suppressing Th1/17 Mediated Inflammation and Promoting Tregs Differentiation in IL-10 Deficient Mice

摘要

Recent studies suggested that excessive T helper (Th)1/17 cells concomitant with regulatory T cell deficiency might play important roles in Crohn's disease. Anti-cluster of differentiation 52 (CD52) monoclonal antibody (mAb), which aims on CD52 antigen on mature immunocytes, has both T cell depletion and immunosuppressive activities. In this study, we evaluated the therapeutic effects and possible mechanisms of anti-CD52 treatment on interleukin-10 (IL-10) deficient mouse. Anti-mouse CD52 mAb was administered to C3H/HeJBir.IL-10(-/-) (C3H center dot IL-10(-/-)) mice intraperitoneally 20 mu g per week for 2 weeks. The disease activity index, body weight, the histological grading of colitis, and levels of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, IL-17 and IL-6 in colon were quantified after treatment. In addition, CD25, Forkhead box P3 (Foxp3) and transforming growth factor (TGF)-beta gene as well as the percentage of CD25(+)Foxp3(+) T cells in colon were also measured. The severity of colitis in IL-10(-/-) mice was significantly decreased by the treatment, with improvement of colon histological grade. The treatment also decreased the TNF-alpha, IL-17 and IL-6 levels in colon. Furthermore, the treatment up-regulated the mRNA expression of CD25, Foxp3 and TGF-beta gene as well as the percentage of CD25(+)Foxp3(+) T cells in colon lamina propria mononuclear cells (LPMCs) of IL-10(-/-) mice. Our data might indicate that anti-CD52 treatment could ameliorate the colitis of C3H center dot IL-10(-/-) mice and it might be related to the suppression of Th1/17 related inflammation and the promotion of regulatory T cell differentiation. Thus, our data reveals that anti-CD52 treatment may hold potential for clinical applications for Crohn's disease treatment.