Decreased expression of microRNA‐21 correlates with the imbalance of Th17 and Treg cells in patients with rheumatoid arthritis

• Published in: Journal of cellular and molecular medicine 2014-11, Vol.18 (11), p.2213-2224
• Main Authors: Dong, Liyang, Wang, Xuefeng, Tan, Jun, Li, Hao, Qian, Wei, Chen, Jianguo, Chen, Qiaoyun, Wang, Jun, Xu, Wenlin, Tao, Caihua, Wang, Shengjun
• Format: Article
• Language: English
• Subjects: Adult; Aged; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Female; Gene Expression Regulation; Humans; Male; MicroRNAs - biosynthesis; MicroRNAs - immunology; Middle Aged; miRNA; Original; pro‐inflammatory cytokine; rheumatoid arthritis; T-Lymphocytes, Regulatory - immunology; Th17; Th17 Cells - immunology; Treg
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12353

The imbalance of Th17/Treg cell populations has been suggested to be involved in the regulation of rheumatoid arthritis (RA) pathogenesis; however, the mechanism behind this phenomenon remains unclear. Recent studies have shown how microRNAs (miRNAs) are important regulators of immune responses and are involved in the development of a variety of inflammatory diseases, including RA. In this study, we demonstrated that the frequencies of CD3+CD4+IL‐17+Th17 cells were significantly higher, and CD4+CD25+FOXP3+ Treg cells significantly lower in peripheral blood mononuclear cells from RA patients. Detection of cytokines from RA patients revealed an elevated panel of pro‐inflammatory cytokines, including IL‐17, IL‐6, IL‐1β, TNF‐α and IL‐22, which carry the inflammatory signature of RA and are crucial in the differentiation and maintenance of pathogenic Th17 cells and dysfunction of Treg cells. However, the level of miR‐21 was significantly lower in RA patients, accompanied by the increase in STAT3 expression and activation, and decrease in STAT5/pSTAT5 protein and Foxp3 mRNA levels. Furthermore, lipopolysaccharide stimulation up‐regulated miR‐21 expression from healthy controls, but down‐regulated miR‐21 expression from RA patients. Therefore, we speculate that miR‐21 may be part of a negative feedback loop in the normal setting. However, miR‐21 levels decrease significantly in RA patients, suggesting that this feedback loop is dysregulated and may contribute to the imbalance of Th17 and Treg cells. MiR‐21 may thus serve as a novel regulator in T‐cell differentiation and homoeostasis, and provides a new therapeutic target for the treatment of RA.