Increasing evidence reveals that long noncoding RNAs (lncRNAs) are associated with autoimmune and inflammatory diseases, such as systemic lupus erythematosus (SLE). In this study, we aimed to explore the role of lncRNA growth arrest specific 5 (GAS5) in the pathogenesis of SLE. We found that lncRNA GAS5 was decreased in CD4⁺ T cells and plasma from SLE patients. Overepression of GAS5 inhibited activation of normal CD4⁺ T cells and attenuated the self-reactivity of SLE CD4⁺ T cells. Additionally, we demonstrated that adenovirus E4 binding protein 4 (E4BP4) was involved in lncRNA GAS5-mediated inhibition of CD4⁺ T cell activation. GAS5 could upregulate E4BP4 by inhibiting miR-92a-3p. Taken together, our results indicate that the GAS5/miR-92a-3p/E4BP4 pathway plays an important role in inhibiting CD4⁺ T cell activation in SLE, thus providing a potential therapeutic target for SLE treatment.

越来越多的证据表明，长链非编码 RNA (lncRNA) 与自身免疫和炎症性疾病有关，例如系统性红斑狼疮 (SLE)。在本研究中，我们旨在探讨 lncRNA 生长停滞特异性 5 (GAS5) 在 SLE 发病机制中的作用。我们发现SLE 患者的CD4 ⁺ T 细胞和血浆中 lncRNA GAS5 降低。GAS5 的过度表达抑制了正常 CD4 ⁺ T 细胞的激活并减弱了 SLE CD4 ⁺ T 细胞的自身反应性。此外，我们证明腺病毒 E4 结合蛋白 4 (E4BP4) 参与了 lncRNA GAS5 介导的 CD4 ⁺T细胞活化。GAS5 可以通过抑制 miR-92a-3p 上调 E4BP4。总之，我们的结果表明 GAS5/miR-92a-3p/E4BP4 通路在抑制SLE 中的CD4 ⁺ T 细胞活化中起重要作用，从而为 SLE 治疗提供了潜在的治疗靶点。