MicroRNA let-7g-5p alleviates murine collagen-induced arthritis by inhibiting Th17 cell differentiation.

Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease with complicated pathogenesis. IL-17-producing T helper cells (Th17) are important players in the RA process. Despite numerous researches have proven that microRNAs (miRNAs) are crucial to regulate autoimmune diseases including RA, the effect of miRNAs on Th17 cell differentiation and function in the RA progress is not clear. Here, our results showed that the expression of miRNA let-7g-5p was substantially lower in RA patients and CIA mice compared with healthy controls, accompanied by the increased Th17 cell population. Furthermore, the inhibition of let-7g-5p on Th17 cell differentiation and function were verified in vitro. Notably, the disease severity in CIA mice was significantly alleviated after the treatment of let-7g-5p mimics. In addition, let-7g-5p mimics treatment markedly down-regulated the frequency of Th17 cells in CIA mice. Taken together, our findings indicate that let-7g-5p can ameliorate CIA through blocking the differentiation of Th17 cells, which may be a novel strategy to treat autoimmune diseases such as RA.

Zishen Tongluo formula ameliorates collagen-induced arthritis in mice by modulation of Th17/Treg balance.

ETHNOPHARMACOLOGICAL RELEVANCE: Zishen Tongluo formula (ZTF) is simplified from the Qingluo Tongbi formula, which has been applied to treat rheumatoid arthritis (RA) in clinical practices for several decades. Our previous studies have verified the effects of ZTF on arthritis animal models. However, its mechanism of treating RA is not clear. AIM OF THE STUDY: The present study was designed to investigate the effects of ZTF on the Th17/Treg balance in RA mice and the role of the different herb groups with the effect of Zishen yangyin (YY), Huatan quyu (HT), or Qufeng chushi (QF) in ZTF. MATERIALS AND METHODS: A mouse model of collagen-induced arthritis (CIA) was established. The animals were randomly divided into the normal, model, positive drug, YY, QF, HT, and the whole compound (ZTF) groups. After oral administration for one-month, cytokine levels in the plasma and histopathological changes of the joint were measured by ELISA and hematoxylin-eosin staining, respectively. Meanwhile, the balance of Th17/Treg cells in blood, spleen or lymph nodes was detected using flow cytometry and qPCR. RESULTS: ZTF or the different functional groups could improve the joint inflammation, decrease the levels of proinflammatory cytokines, restore the balance of Th17 and Treg cells in CIA mice. However, there were some differences in each functional group: YY mainly promoted the responses of Treg cells while QF inhibited the functions of Th17 cells. Besides, HT regulated both Th17 and Treg cells to keep the immune balance. CONCLUSIONS: ZTF could notably ameliorate CIA mice by restoring the balance of Th17/Treg cells. Each functional group could target Th17 and/or Treg cells to produce synergistic/enhancement effects, and ZTF had a better holistic effect in RA treatment.

Th17 cell pathogenicity and plasticity in rheumatoid arthritis.

CD4+ Th cells play an important role in the development of rheumatoid arthritis (RA) by regulating adaptive immune response. As major subsets of CD4+ Th cells, Th17 cells can produce a large number of hallmark cytokines such as IL-17A and IL-17F, which participate in host defense and immune homeostasis. However, increasing researches have shown that Th17 cells are unstable and exhibit a certain degree of plasticity, which aggravates their pathogenicity. Furthermore, the plasticity and pathogenicity of Th17 cells are closely related with the disease activity in RA. In this paper, the characteristics including phenotype, differentiation, plasticity, and pathogenicity of Th17 cells in RA will be systematically summarized. This will contribute to clarify the immunologic mechanism of RA and further provide a novel strategy for the clinical treatment of autoimmune diseases.