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 June 1, 2018; First published May 14, 2018
Citation Information: J Clin Invest. 2018;128(6):2551-2568. https://doi.org/10.1172/JCI97426.
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Categories: 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 1

miR-210 expression is elevated in psoriatic CD4+ T cells and skin lesions.

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miR-210 expression is elevated in psoriatic CD4+ T cells and skin lesion...
(A and B) Expression of miR-210 in CD4+ T cells (A, n = 30) and skin samples (B, n = 10) derived from psoriasis patients and healthy controls. (C and D) Correlation of human miR-210 expression in psoriatic CD4+ T cells (C, n = 30) or skin (D, n = 10) with PASI scores. (E) Expression of miR-210 in splenic CD4+ T cells (left panel) and skin samples (right panel) from untreated mice (n = 6) and IMQ-induced mice (n = 6). (F) Expression of miR-210 in skin lesions from normal ears (n = 5) and IL-23–treated ears (n = 5) of mice. (G) In situ hybridization was performed on mouse skin treated with vehicle (Ctr, n = 5) or IMQ (IMQ, n = 5) as well as human skin from healthy controls (NC, n = 6) and psoriasis patients (Pso, n = 5) using miR-210–specific LNA probes. Dark blue color indicates miR-210 expression. e, epidermis; d, dermis. Scale bars: 100 μm (lower magnification) and 50 μm (higher magnification). Red arrows indicate dermis-infiltrating inflammatory cells. (H) Expression of miR-210 in the epidermis and dermis of skin samples from untreated controls (n = 6) or IMQ-treated mice (n = 6). (I) miR-210 levels in CD4+ T cells derived from untreated mouse spleen (n = 6), IMQ-treated mouse spleen (n = 6), and IMQ-treated mouse lesional dermis (n = 6). (J) Expression of miR-210 in dermal CD4– T cells of skin samples from untreated controls (n = 6) or IMQ-treated mice (n = 6). Data are pooled from 2 independent experiments (A–D) or are representative of 3 independent experiments (E–J) in BALB/c mice (E and G–J) and in C57BL/6J mice (F). Data represent the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001. Two-tailed Mann-Whitney U test (A and B), 2-tailed unpaired Student’s t test (E, F, and J), Spearman’s r test (C and D), or 1-way ANOVA with Bonferroni’s post hoc test (H and I) was used.