Circular RNAs (circRNAs) regulate gene expression and participate in various biological and pathological processes. However, little is known about the effects of specific circRNAs on T helper cell 17 (Th17) differentiation and related autoimmune diseases, such as multiple sclerosis (MS). Here, using transcriptome microarray analysis at different stages of experimental autoimmune encephalomyelitis (EAE), we identified the EAE progression-related circINPP4B, which showed upregulated expression in Th17 cells from mice with EAE and during Th17 differentiation in vitro. Silencing of circINPP4B inhibited Th17 differentiation and alleviated EAE, characterized by less demyelination and Th17 infiltration in the spinal cord. Mechanistically, circINPP4B served as a sponge that directly targeted miR-30a to regulate Th17 differentiation. Furthermore, circINPP4B levels were associated with the developing phases of clinical relapsing-remitting MS patients. Our results indicate that circINPP4B plays an important role in promoting Th17 differentiation and progression of EAE by targeting miR-30a, which provides a potential diagnostic and therapeutic target for Th17-mediated MS.

环状 RNA (circRNA) 调节基因表达并参与各种生物学和病理过程。然而，关于特定 circRNAs 对 T 辅助细胞 17 (Th17) 分化和相关自身免疫性疾病如多发性硬化症 (MS) 的影响知之甚少。在这里，使用实验性自身免疫性脑脊髓炎 (EAE) 不同阶段的转录组微阵列分析，我们确定了 EAE 进展相关的 circINPP4B，它在 EAE 小鼠的 Th17 细胞和体外 Th17 分化过程中表现出上调的表达。circINPP4B 的沉默抑制了 Th17 分化并减轻了 EAE，其特征是脊髓中较少的脱髓鞘和 Th17 浸润。从机制上讲，circINPP4B 作为海绵直接靶向 miR-30a 以调节 Th17 分化。此外，circINPP4B 水平与临床复发缓解型 MS 患者的发展阶段相关。我们的研究结果表明，circINPP4B 通过靶向 miR-30a 在促进 EAE 的 Th17 分化和进展中发挥重要作用，这为 Th17 介导的 MS 提供了潜在的诊断和治疗靶点。