In psoriasis, environmental triggers skew T cell differentiation toward Th1 and Th17 subsets, which release proinflammatory cytokines that play a key role in this condition’s pathogenesis. Monoclonal antibodies targeting the cytokine cascade can improve psoriasis, but the root cause of pathogenic T cell imbalance remains unclear. A study led by Qianjin Lu and the Central South University in Hunan, China followed up on reports of miR-210 upregulation in psoriasis patients. The study, published last week in the JCI, shows that increased miR-210 expression enhances Th1 and Th17 differentiation and facilitates psoriasis-like inflammation. The researchers determined that miR-210 represses its targets, STAT6 and LYN, to bias the immune response toward pathogenic T cell subsets. Ablation or silencing of miR-210 protected against psoriasis development in a mouse model, suggesting a potential strategy for preventing T cell imbalances that contribute to psoriatic inflammation.
The highlighted image illustrates the imbalance between CD4+ T cell subsets (red) in a human psoriatic lesion, with numerous Th1 cells (co-stained for T-bet, yellow) and Th17 cells (co-stained for IL-17, blue) and few Tregs (co-stained for Foxp3, cyan). Nuclei are shown in white (DAPI). Image credit: Dr. Qianwen Li, Hunan Key Laboratory of Medical Epigenetics.
Immune imbalance of T lymphocyte subsets is a hallmark of psoriasis, but the molecular mechanisms underlying this aspect of psoriasis pathology are poorly understood. Here, we report that microRNA-210 (miR-210), a miR that is highly expressed in both psoriasis patients and mouse models, induces helper T (Th) 17 and Th1 cell differentiation but inhibits Th2 differentiation through repressing STAT6 and LYN expression, contributing to several aspects of the immune imbalance in psoriasis. Both miR-210 ablation in mice and inhibition of miR-210 by intradermal injection of antagomir-210 blocked the immune imbalance and the development of psoriasis-like inflammation in an imiquimod-induced or IL-23–induced psoriasis-like mouse model. We further showed that TGF-β and IL-23 enhance miR-210 expression by inducing HIF-1α, which recruits P300 and promotes histone H3 acetylation in the miR-210 promoter region. Our results reveal a crucial role for miR-210 in the immune imbalance of T lymphocyte subsets in psoriasis and suggest a potential therapeutic avenue.
Ruifang Wu, Jinrong Zeng, Jin Yuan, Xinjie Deng, Yi Huang, Lina Chen, Peng Zhang, Huan Feng, Zixin Liu, Zijun Wang, Xiaofei Gao, Haijing Wu, Honglin Wang, Yuwen Su, Ming Zhao, Qianjin Lu