MicroRNA-210 overexpression promotes psoriasis-like inflammation by inducing Th1 and Th17 cell differentiation
Ruifang Wu, … , Ming Zhao, Qianjin Lu
Ruifang Wu, … , Ming Zhao, Qianjin Lu
Published May 14, 2018
Citation Information: J Clin Invest. 2018;128(6):2551-2568. https://doi.org/10.1172/JCI97426.
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Research Article Autoimmunity Dermatology

MicroRNA-210 overexpression promotes psoriasis-like inflammation by inducing Th1 and Th17 cell differentiation

Abstract

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.

Authors

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

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Figure 2

miR-210 contributes to the altered balance between pathogenic Th1/Th17 cells and Th2 cells in psoriasis.

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miR-210 contributes to the altered balance between pathogenic Th1/Th17 c...
(A) miR-210 expression in naive CD4+ T, Th0, Th1, Th2, Th17, and iTreg cells (n = 5). (B) miR-210 expression in CD4+ T cells transfected with agomir-210 (n = 3) or antagomir-210 (n = 3). (C and D) Human naive CD4+ T cells were transfected with agomir-210 (C, n = 3), antagomir-210 (D, n = 3), or their corresponding controls and then were differentiated into Th1, Th2, Th17, and iTreg cells. The percentage of Th1, Th2, Th17, and iTreg cells was detected by flow cytometry. Statistical analysis data are shown in the lower panel. (E and F) The protein levels of IL-17A, IL-17F, IFN-γ, and IL-4 in cultured supernatants from normal human CD4+ T cells transfected with agomir-210 or agomir-NC (E, n = 6) and psoriatic CD4+ T cells transfected with antagomir-210 or antagomir-NC (F, n = 6). (G and H) The mRNA levels of IL17A, IL17F, IFNG, and IL4 in normal human CD4+ T cells transfected with agomir-210 or agomir-NC (G, n = 6) and psoriatic CD4+ T cells transfected with antagomir-210 or antagomir-NC (H, n = 6). All experiments were performed in triplicate. Data represent the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001. NS, not significant. One-way ANOVA with Dunnett’s post hoc test (A) or 2-tailed unpaired Student’s t test (B–H) was used.