The immunoglobulin D Fc receptor expressed on fibroblast-like synoviocytes from patients with rheumatoid arthritis contributes to the cell activation
The immunoglobulin D Fc receptor expressed on fibroblast-like synoviocytes from patients with rheumatoid arthritis contributes to the cell activation
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类风湿性关节炎患者的成纤维样滑膜细胞上表达的免疫球蛋白 D Fc 受体有助于细胞活化
DOI：
10.1038/aps.2017.105
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发表时间：
2017
影响因子：
8.2
通讯作者：
Wei W
中科院分区：
文献类型：
--
作者：
Wu Yu-jing;Chen Wen-sheng;Chen Heng-shi;Dai Xing;Dong Jin;Wang Ying;Zhang Ling-ling;Chang Yan;Huang Qiong;Jia Xiao-yi;Wei Wei;Wei W
免疫球蛋白IgD可能在自身免疫性疾病中发挥重要作用，但IgD的功能仍然难以捉摸，尽管多次尝试确定其生物学功能。纤维母细胞样滑膜细胞（FLSs）是滑膜的特化细胞，在类风湿关节炎（RA）的发病过程中起关键作用。在这项研究中，我们探讨了IgD过度表达对RA患者FLSs （RA-FLSs）功能的可能作用。我们发现IgD Fc受体（IgDR）在FLSs上组成性表达，与健康对照（HC-FLSs）制备的FLSs相比，RA-FLSs中的IgD Fc受体（IgDR）显著升高。此外，IgDR主要存在于细胞表面和细胞质中。我们进一步检测了IgD与IgDR在HC-FLSs上的内在结合亲和力，平衡解离常数（kd）为0.067 nmol/L。RA-FLSs与IgD （1-10 μg/mL）孵育48 h，剂量依赖性地促进IgDR的表达，刺激炎症因子和趋化因子如IL-1β、IL-6、单核细胞趋化蛋白(MCP)-1、TNF-α和核因子-κB配体受体激活剂（RANKL）的产生，从而可能促进IgD-IgDR交联。此外，IgD （0.1 ~ 10 μg/mL）孵育48 h，可增强HC-FLSs和RA-FLSs的活力。我们的研究结果表明，IgDR在RA-FLSs上表达，并有助于FLSs的激活，这表明IgD-IgDR是治疗RA的潜在的新的免疫治疗靶点。
Immunoglobulin IgD might play an important role in autoimmune diseases, but the function of IgD has remained elusive, despite multiple attempts to define its biological function. Fibroblast-like synoviocytes (FLSs) are specialized cells of the synovium that play a key role in the pathogenesis of rheumatoid arthritis (RA). In this study we explored the possible roles of excessive IgD expression on the function of FLSs from RA patients (RA-FLSs). We showed that IgD Fc receptor (IgDR) was constitutively expressed on FLSs, and was significantly elevated in RA-FLSs compared with FLSs prepared from synovial tissues of healthy controls (HC-FLSs). Furthermore, IgDR was mainly detected on the cell surface and in the cytoplasm. We further detected the intrinsic binding affinity of IgD to IgDR on HC-FLSs with an equilibrium dissociation constant (K D) of 0.067 nmol/L. Incubation of RA-FLSs with IgD (1–10 μg/mL) for 48 h dose-dependently promoted the expression of IgDR, and stimulated the production of inflammatory cytokines and chemokines, such as IL-1β, IL-6, monocyte chemotactic protein (MCP)-1, TNF-α and receptor activator of nuclear factor-κB ligand (RANKL), thus potentially contributing to IgD-IgDR crosslinking. Moreover, incubation with IgD (0.1–10 μg/mL) for 48 h dose-dependently enhanced viability for both HC-FLSs and RA-FLSs. Our results demonstrate that IgDR is expressed on RA-FLSs and contributes to the activation of FLSs, and suggest that IgD-IgDR is a potential novel immunotherapeutic target for the management of RA.