Abstract
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.
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Acknowledgments
We thank the Affiliated Hospital to Bengbu Medical college for the capital and equipment support.
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This work was supported by the Nature Science Key Program of Bengbu Medical College (no. BYKY1852ZD).
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Jian Wang, Xin Wang, and Longfei Wang performed the experiments. Jian Wang, Xin Wang, and Zhijun Li analyzed data. Longfei Wang, Chao Sun, Changhao Xie, and Zhijun Li contributed reagents/materials/analysis tools. Jian Wang, Xin Wang, and Zhijun Li wrote the manuscript. All authors discussed the results and commented on the manuscript.
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Editor: Tetsuji Okamoto
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Wang, J., Wang, X., Wang, L. et al. MiR-let-7d-3p regulates IL-17 expression through targeting AKT1/mTOR signaling in CD4+ T cells. In Vitro Cell.Dev.Biol.-Animal 56, 67–74 (2020). https://doi.org/10.1007/s11626-019-00409-5
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DOI: https://doi.org/10.1007/s11626-019-00409-5