Identification of novel rheumatoid arthritis-associated MiRNA-204-5p from plasma exosomes

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.

Rheumatoid arthritis: Possible microRNA biomarker identified

A microRNA that is significantly reduced in joint tissues in rheumatoid arthritis could provide a therapeutic target and act as a biomarker for disease progression. In rheumatoid arthritis, immune cells release exosomes, tiny vesicles containing microRNA and proteins that are transferred to cells in the synovium, the connective tissue lining the inside of the joint capsule. This transfer of molecules influences synovial cell activity. Shu-Feng Lei and Fei-Yan Deng at the Medical School of Soochow University, Suzhou, China, and co-workers identifed exosomal microRNAs present in rheumatoid arthritis, and examined their effect on synovial cells. Levels of one exosomal microRNA, miR-204-5p, were significantly lower in patient samples and mice models, inversely correlating with disease severity. The team believe that chronic inflammation may suppress levels of miR-204-5p. Treatment boosting microRNA levels in mice models slowed disease progression.