Department of Clinical Immunology, PLA Specialized Research Institute of Rheumatology & Immunology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
National Translational Science Center for Molecular Medicine & Department of Cell Biology, The Fourth Military Medical University, Xi'an, China.
Front Immunol. 2020 Oct 28;11:545980. doi: 10.3389/fimmu.2020.545980. eCollection 2020.
Rheumatoid arthritis (RA) is a common autoimmune disease in which T helper-type 17 (Th17) cells have been critically involved. CD147 is a T cell activation-associated molecule and is involved in T cell development. However, it remains unclear whether CD147 participates in Th17 responses in RA patients. In this study, we demonstrated that in both the RA and healthy controls (HC) groups, CD147 expression on CD4 T cells was increased in CCR6 and CD161 subsets, and was associated with IL-17 production. Ligation of CD147 with its monoclonal antibody (mAb) strongly inhibited Th17 responses, and knock down of CD147 expression on CD4 Tm cells specifically enhanced Th17 responses, triggered by coculture with activated monocytes from HC. Further functional studies showed that anti-CD147 mAb decreased the activation of AKT, mTORC1 and STAT3 signaling, which is known to enhance Th17 responses. Ligation of CD147 with its mAb on CD4 Tm cells specifically reduced Th17 responses induced by or activated monocytes from RA patients. In collagen-induced arthritis model, anti-CD147 mAb treatment reduced the Th17 levels and severity of arthritis . These data suggest that CD147 plays a negative role in regulating human Th17 responses. Anti-CD147 mAb can limit the extraordinary proliferation of Th17 cells and may be a new therapeutic option in RA.
类风湿关节炎（RA）是一种常见的自身免疫性疾病，其中 T 辅助细胞 17（Th17）细胞被认为是关键因素。CD147 是一种 T 细胞激活相关分子，参与 T 细胞的发育。然而，目前尚不清楚 CD147 是否参与 RA 患者的 Th17 反应。在本研究中，我们发现，在 RA 患者和健康对照者（HC）中，CD4 T 细胞上的 CD147 表达在 CCR6 和 CD161 亚群中增加，并与 IL-17 的产生相关。用其单克隆抗体（mAb）交联 CD147 强烈抑制 Th17 反应，并且敲低 CD4 Tm 细胞上的 CD147 表达特异性增强了来自 HC 的激活单核细胞共培养触发的 Th17 反应。进一步的功能研究表明，抗 CD147 mAb 降低了 AKT、mTORC1 和 STAT3 信号通路的激活，这些信号通路已知能增强 Th17 反应。用其 mAb 交联 CD4 Tm 细胞上的 CD147 特异性降低了来自 RA 患者的 或 激活单核细胞诱导的 Th17 反应。在胶原诱导的关节炎模型中，抗 CD147 mAb 治疗降低了 Th17 水平和关节炎的严重程度。这些数据表明 CD147 在调节人类 Th17 反应中发挥负性作用。抗 CD147 mAb 可以限制 Th17 细胞的异常增殖，可能是 RA 的一种新的治疗选择。
