Jiangsu Key Laboratory of Druggability of Biopharmaceuticals and State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China.
School of Basic Medicine, Jinan University, Guangzhou, 510632, China.
Mol Immunol. 2020 Sep;125:32-42. doi: 10.1016/j.molimm.2020.06.027. Epub 2020 Jul 3.
Compelling evidence has demonstrated that Th17 cells play an essential role in the pathogenesis of multiple sclerosis (MS). Long noncoding RNAs (lncRNAs) have been confirmed as vital regulators of immune cell differentiation and other functions. However, whether and how lncRNAs influence Th17 cell differentiation and functional behaviors remain largely unclear. Here, we identified that a lncRNA, namely Gm15575, is specifically enriched in Th17 cells and spleen tissues of EAE mice. Functionally, knockdown of Gm15575 in Th17 cells suppressed the secretion of IL17A. Mechanistically, Gm15575 served as a competing endogenous RNA (ceRNA) to block the function of miR-686, positively regulating the expression of CCL7, a pro-inflammatory chemokine with high expression in Th17 cells, and Th17 differentiation. Taken together, our study revealed that Gm15575-miR-686 axis promoted the progression of EAE by regulating Th17 differentiation and expression of CCL7 which elucidated the pathogenesis of autoimmune diseases at genetic level. Gm15575 can be involved in the course of Th17-related autoimmune diseases.
大量证据表明，Th17 细胞在多发性硬化症（MS）的发病机制中起关键作用。长链非编码 RNA（lncRNA）已被证实是免疫细胞分化和其他功能的重要调节因子。然而，lncRNA 是否以及如何影响 Th17 细胞分化和功能行为仍很大程度上不清楚。在这里，我们鉴定出一个 lncRNA，即 Gm15575，在 Th17 细胞和 EAE 小鼠的脾脏组织中特异性富集。功能上，在 Th17 细胞中敲低 Gm15575 抑制了 IL17A 的分泌。机制上，Gm15575 作为竞争性内源 RNA（ceRNA），阻断了 miR-686 的功能，正向调节 CCL7 的表达，CCL7 是 Th17 细胞中高表达的促炎趋化因子，促进 Th17 分化。总之，我们的研究表明，Gm15575-miR-686 轴通过调节 Th17 分化和 CCL7 的表达促进 EAE 的进展，从遗传水平阐明了自身免疫性疾病的发病机制。Gm15575 可能参与 Th17 相关自身免疫性疾病的病程。
