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.
View: Text | PDF
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

×

Figure 6

STAT6 and LYN are downstream targets of miR-210.

Options: View larger image (or click on image) Download as PowerPoint
STAT6 and LYN are downstream targets of miR-210. (A) miR-210 target sequ...
(A) miR-210 target sequences (in red) of the 3′-UTR of STAT6 (A, upper panel) and LYN (A, lower panel) mRNAs and corresponding mutant sequences, which were included in luciferase reporter vectors. (B) Luciferase activities were measured in HEK293T cells cotransfected with luciferase reporter vectors and agomir-210 or agomir-NC, n = 3 per group. (C) Normal CD4+ T cells were transfected with agomir-210 or agomir-NC, and psoriatic CD4+ T cells were transfected with antagomir-210 or antagomir-NC. STAT6 (upper panel) and LYN (lower panel) protein levels were analyzed. (D) The protein levels of STAT6 and LYN in splenic CD4+ T cells from IMQ-treated WT and KO mice. (E–H) STAT6 and LYN protein levels in CD4+ T cells (E and F) and skin lesions (G and H) derived from psoriasis patients and IMQ-induced psoriasis-like mouse models (BALB/c) as well as their healthy controls. Data (B and C) are representative of at least 3 independent experiments. Data represent the mean ± SEM. *P < 0.05, **P < 0.01. NS, not significant. Two-tailed unpaired Student’s t test (B) was used.