The aberrant expression of interleukin-17 (IL-17) has been reported in the pathogenesis of autoimmune diseases, such as primary Sjögren's syndrome (pSS). However, the detailed mechanism remains poorly understood. We aim to characterize the expression of IL-17 in pSS and analyze the detailed underlying mechanism. IL-17 and microRNA miR-let-7d-3p expression were assayed by quantitative real-time PCR and Western blot, and proliferation-related protein expression was measured by Western blot. Luciferase reporter assays were performed to detect the direct regulation of IL-17 by miR-let-7d-3p. Expression of miR-let-7d-3p was negatively correlated with the expression of IL-17 in patients with pSS. Besides, the AKT1/mTOR signaling pathway was found critical for miR-let-7d-3p-mediated IL-17 expression. Furthermore, miR-let-7d-3p targeted AKT1 to bridge the regulation of IL-17. Finally, we verified AKT1 co-expression could rescue IL-17 downregulation caused by miR-let-7d-3p. Our study revealed novel mechanism that how did IL-17 was exactly modulated by miR-let-7d-3p and the potential of miR-let-7d-3p-AKT1-mTOR-IL-17 signaling as therapeutic targets for autoimmune diseases.

中文翻译：

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MiR-let-7d-3p通过靶向CD4 + T细胞中的AKT1 / mTOR信号传导来调节IL-17表达。

白细胞介素17（IL-17）的异常表达已被报道在自身免疫性疾病的发病中，如原发性干燥综合征（pSS）。但是，详细的机制仍然知之甚少。我们旨在表征IL-17在pSS中的表达，并分析其详细的潜在机制。通过定量实时PCR和Western blot检测IL-17和microRNA miR-let-7d-3p的表达，并通过Western blot检测增殖相关蛋白的表达。进行荧光素酶报告基因测定以检测miR-let-7d-3p对IL-17的直接调节。在pSS患者中，miR-let-7d-3p的表达与IL-17的表达呈负相关。此外，发现AKT1 / mTOR信号通路对于miR-let-7d-3p介导的IL-17表达至关重要。此外，miR-let-7d-3p靶向AKT1以桥接IL-17的调控。最后，我们证实AKT1共表达可以挽救miR-let-7d-3p引起的IL-17下调。我们的研究揭示了新的机制，即miR-let-7d-3p如何精确调控IL-17以及miR-let-7d-3p-AKT1-mTOR-IL-17信号转导作为自身免疫性疾病治疗靶点的潜力。