The immunoglobulin D Fc receptor expressed on fibroblast-like synoviocytes from patients with rheumatoid arthritis contributes to the cell activation

• 来源期刊: 中国药理学报（英文版）
• 关键词: rheumatoid arthritis immunoglobulin D immunoglobulin D Fc receptor fibroblast-like synoviocytes fluorescence based receptor binding assay inflammatory cytokines
• 年，卷（期）: 2017,（11）
• 页码范围: 1466-1474
• 页数: 9页
• 语种: 英文
• DOI: 10.1038/aps.2017.105

摘要

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 (KD) of 0.067 nmol/L.Incubation of RA-FLSs with IgD (1-10 μg/mL) for 48 h dosedependently 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.