RA成纤维样滑膜细胞DC-SIGN在B细胞活化中的作用及其临床意义

B细胞异常活化在类风湿关节炎（RA）发病中起关键作用。滑膜炎症是RA基本病理变化，成纤维样滑膜细胞（FLS）是其中重要效应细胞，但RA FLS与B细胞异常活化的关系不清。我们前期研究发现，RA FLS可促进B细胞的增殖与活化；RA FLS中DC-SIGN高表达，DC-SIGN中和抗体可阻断RA FLS对B细胞的激活作用。本课题拟通过解决“RA FLS是否通过DC-SIGN激活B细胞？以及RA患者行膝关节滑膜切除术能否抑制B细胞活化防止病情复发？”这些关键科学问题，来验证科学假说：RA FLS通过DC-SIGN参与B细胞异常活化过程，对FLS高表达DC-SIGN的RA患者行膝关节滑膜切除术可抑制B细胞活化防止病情复发。将主要采用DC-SIGN条件性基因敲除小鼠等方法，及对拟接受膝关节滑膜切除术的RA患者进行前瞻性研究，为准确把握膝关节滑膜切除术手术指征提供科学依据。

Abnormal activation of B cells plays a key role in the pathogenesis of rheumatoid arthritis (RA). Synovial inflammation is the basic pathological change of RA, among which fibroblast-like synovial cells (FLS) are the mportant effector cells, but the relationship between RA FLS and abnormal activation of B cells is unclear. Our previous study found that RA FLS can promote the proliferation and activation of B cells. DC-SIGN is highly expressed in RA FLS, and DCS-SIGN neutralizing antibody can block the activation of B cells by RA FLS. The project aims to address the two key scientific issues, namely, whether RA FLS activates B cells through DC-SIGN and whether synovectomy of the knee joint can inhibit the activation of B cells in RA patients to prevent disease recurrence, to verify the scientific hypothesis that RA FLS participates in the abnormal activation of B cells through DC-SIGN, and synovectomy of the knee joint for RA patients with high expression of DC-SIGN in FLS can inhibit the activation of B cells and prevent disease recurrence. This project will mainly adopt the methods of DC-SIGN conditional knockout mice, and conduct a prospective study on RA patients who plan to receive synovectomy of the knee joint so as to provide a scientific basis for accurately grasping the indications of synovectomy of the knee joint and carrying out the precise treatment of RA.