We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
MicroRNA-30a controls the instability of inducible CD4<sup>+</sup> Tregs through SOCS1.
- Authors
Zhou, Ya; Li, Yongju; Lu, Jia; Hong, Xiaowu; Xu, Lin
- 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.
- Subjects
CYTOTOXIC T lymphocyte-associated molecule-4; TUMOR necrosis factor receptors; SUPPRESSOR cells; CYTOTOXIC T cells; GLUCOCORTICOIDS; IMMUNOREGULATION; CELL physiology; T cells
- Publication
Molecular Medicine Reports, 2019, Vol 20, Issue 5, p4303
- ISSN
1791-2997
- Publication type
Article
- DOI
10.3892/mmr.2019.10666