MiR-let-7d-3p regulates IL-17 expression through targeting AKT1/mTOR signaling in CD4⁺ T cells

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 und...

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Bibliographic Details
Published in:In vitro cellular & developmental biology. Animal 2020-01, Vol.56 (1), p.67-74
Main Authors: Wang, Jian, Wang, Xin, Wang, Longfei, Sun, Chao, Xie, Changhao, Li, Zhijun
Format: Article
Language:English
Subjects:
AKT1 protein
Animal Genetics and Genomics
Autoimmune diseases
Biomedical and Life Sciences
CD4 antigen
Cell Biology
Cell Culture
CELLULAR PATHOLOGY/VIROLOGY
Developmental Biology
Interleukin 17
Interleukins
Life Sciences
Lymphocytes
Lymphocytes T
miRNA
Pathogenesis
Ribonucleic acid
RNA
Signal transduction
Signaling
Sjogren's syndrome
Stem Cells
Therapeutic applications
TOR protein
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Summary: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.
ISSN:1071-2690
1543-706X
DOI:10.1007/s11626-019-00409-5