MicroRNA‑30a controls the instability of inducible CD4+ Tregs through SOCS1

Zhou,Ya; Li,Yongju; Lu,Jia; Hong,Xiaowu; Xu,Lin

doi:10.3892/mmr.2019.10666

MicroRNA‑30a controls the instability of inducible CD4+ Tregs through SOCS1

Authors:
- Ya Zhou
- Yongju Li
- Jia Lu
- Xiaowu Hong
- Lin Xu
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Affiliations: Department of Medical Physics, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China, Special Key Laboratory of Gene Detection and Therapy of Guizhou Province, Zunyi, Guizhou 563000, P.R. China, Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Published online on: September 10, 2019 https://doi.org/10.3892/mmr.2019.10666
Pages: 4303-4314

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Abstract

Inducible regulatory T cells (iTregs) are an important subset of Tregs and play a role in the maintenance of peripheral tolerance, and the occurrence of a number of diseases, including tumors and autoimmune diseases. However, the instability of iTregs is a major obstacle for their potential application in clinical trials. The underlying mechanism of iTreg instability remains largely unknown. In the present study, the expression level of microRNA (miRNA/miR)‑30a in murine iTregs was evaluated using reverse transcription‑quantitative PCR. miR‑30a mimics and a miR‑negative control (NC) were transiently transfected into iTregs using Nucleofector technology. The effects of miR‑30a on the suppressive function of murine iTregs in vitro and in vivo were investigated using MTT, adoptive cell transfer (ACT) and flow cytometry assays, as well as a murine model of lung cancer. In the present study, it was identified that the expression level of miR‑30a was lower in murine iTregs in vitro compared with natural (n)Tregs. Furthermore, compared with miR‑NC, miR‑30a mimics impaired the suppressive function of murine iTregs on murine CD4+ T cell proliferation in vitro, which was accompanied by the altered expression of cytotoxic T lymphocyte‑associated antigen 4 and glucocorticoid induced tumor necrosis factor receptor, as well as transforming growth factor‑β and interleukin‑10. It was also observed that, compared with miR‑NC, miR‑30a mimics abrogated the suppressive effects of murine iTregs on murine CD8+ T cell function in vivo, producing an effective antitumor effect in mice bearing 3LL lung cancer cells in the ACT assay. From a mechanistic point, the expression level of suppressor of cytokine signaling 1, a putative target of miR‑30a, was elevated, altering the activation of the Akt and STAT1 pathway in the miR‑30a mimic transfected group compared with the miR‑NC group, reducing the suppressive function of murine iTregs. The present study identified a role for miR‑30a in the instability of iTregs and provided a novel insight into the development of therapeutic strategies for promoting T‑cell immunity via the regulation of iTreg instability by targeting specific miRNAs.

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