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.

有力的证据表明，Th17细胞在多发性硬化症（MS）的发病机理中起着至关重要的作用。长非编码RNA（lncRNA）已被确认为免疫细胞分化和其他功能的重要调节剂。然而，lncRNAs是否以及如何影响Th17细胞分化和功能行为仍不清楚。在这里，我们确定了lncRNA，即Gm15575，在Th17细胞和EAE小鼠的脾脏组织中特异性富集。从功能上讲，在Th17细胞中敲除Gm15575可以抑制IL17A的分泌。从机制上讲，Gm15575充当竞争性内源RNA（ceRNA）来阻止miR-686的功能，积极调节CCL7的表达，CCL7是在Th17细胞中高表达并促Th17分化的促炎性趋化因子。在一起 我们的研究表明，Gm15575-miR-686轴通过调节Th17分化和CCL7的表达促进了EAE的发展，从基因水平阐明了自身免疫性疾病的发病机理。Gm15575可能与Th17相关的自身免疫性疾病有关。