MicroRNA-210 overexpression promotes psoriasis-like inflammation by inducing Th1 and Th17 cell differentiation
MicroRNA-210 overexpression promotes psoriasis-like inflammation by inducing Th1 and Th17 cell differentiation
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MicroRNA-210过表达通过诱导Th1和Th17细胞分化促进银屑病样炎症
DOI：
10.1172/jci97426
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发表时间：
2018-06-01
影响因子：
15.9
通讯作者：
Lu, Qianjin
中科院分区：
文献类型：
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作者：
Wu, Ruifang;Zeng, Jinrong;Lu, Qianjin
T淋巴细胞亚群免疫失衡是银屑病的一个标志，但银屑病发病的分子机制尚不清楚。在这里，我们报道了microRNA-210(miR-210)，一种在银屑病患者和小鼠模型中高度表达的miR，通过抑制STAT6和Lyn的表达，诱导辅助T(Th)17和Th1细胞分化，但抑制Th2分化，导致银屑病免疫失衡的几个方面。消融小鼠的miR-210和皮内注射antagomir-210抑制miR-210均可阻止咪喹莫特或IL-23诱导的银屑病样小鼠模型的免疫失衡和银屑病样炎症的发展。我们进一步证明，转化生长因子-1和IL-23通过诱导HIF-1和AgR-1促进miR-210的表达，从而招募P300并促进miR-210启动子区域的组蛋白H3乙酰化。我们的结果揭示了miR-210在银屑病T淋巴细胞亚群免疫失衡中的关键作用，并提示了一种潜在的治疗途径。
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-&bgr; and IL-23 enhance miR-210 expression by inducing HIF-1&agr;, 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.