External Innovation, Sumitomo Dainippon Pharma Co., Ltd, Osaka, 554-0022, Japan.
Applied Bioscience Group, Bioscience Research Laboratory, Sumitomo Chemical Co., Ltd, Osaka, 554-0022, Japan.
Sci Rep. 2020 Apr 24;10(1):6969. doi: 10.1038/s41598-020-64012-5.
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.
炎症性肠病(IBD)是一种与肠道中 CD4 T 细胞活化相关的免疫性疾病。CD81 是免疫系统的调节剂,具有多种生物学功能。因此,在本研究中,我们评估了 CD81 对 IBD 病理生理学的贡献以及抗 CD81 抗体的治疗效果。体外培养的活化 T 细胞和体内结肠炎小鼠中 CD81 的表达增加。我们评估了抗 CD81 抗体在结肠炎小鼠中的治疗效果,包括抗体的长期效果。用抗 CD81 抗体治疗可改善结肠炎评分、减轻结肠缩短、降低体重减轻,并减少结肠炎小鼠结肠的病理变化。此外,抗 CD81 抗体降低了结肠炎小鼠血液中升高的炎症标志物。抗 CD81 抗体治疗对结肠炎小鼠具有持久的治疗效果,甚至在停止治疗后仍有效。两种不同的抗鼠 CD81 抗体克隆在结肠炎小鼠中也有效。此外,抗 CD81 抗体减少了结肠炎小鼠和体外 CD4 T 细胞的迁移。因此,CD81 有助于 IBD 发病机制,用抗 CD81 抗体治疗可能是 IBD 患者的一种潜在新型治疗方法。