Abstract
Inflammatory bowel disease (IBD) is an immunological disease associated with CD4+ T cell activation in the intestines. CD81 is a regulator of the immune system with multiple biological functions. Therefore, in this study, we assessed the contribution of CD81 to IBD pathophysiology and the therapeutic efficacy of anti-CD81 antibodies. Expression of CD81 was increased on activated T cells in vitro and in colitic mice in vivo. Therapeutic effects of anti-CD81 antibodies on colitic symptoms and inflammation were evaluated in mice with colitis, including long-term effects of the antibodies. Treatment with anti-CD81 antibodies improved colitis scores, reduced colon shortening, decreased loss of body weight, and resulted in fewer pathological changes of the colon in colitic mice. Moreover, the increased inflammatory markers in the blood of colitic mice were decreased by anti-CD81 antibodies. The anti-CD81 antibody treatment had long-lasting therapeutic effects on colitic mice, even after cessation of treatment. Two different clones of the anti-mouse CD81 antibody were also effective in mice with colitis. Furthermore, anti-CD81 antibodies reduced migration of CD4+ T cells both in colitic mice and in vitro. Thus, CD81 contributes to IBD pathology and treatment with anti-CD81 antibodies may be a potential novel therapy for IBD patients.