MicroRNA-125a-5p regulates the effect of Tregs on Th1 and Th17 through targeting ETS-1/STAT3 in psoriasis

J Transl Med. 2023 Sep 29;21(1):678. doi: 10.1186/s12967-023-04427-6.

Abstract

Background: Psoriasis is an inflammatory disease mediated by helper T (Th)17 and Th1 cells. MicroRNA-125a (miR-125a) is reduced in the lesional skin of psoriatic patients. However, the mechanism by which miR-125a participates in psoriasis remains unclear.

Methods: The levels of miR-125a-5p and its downstream targets (ETS-1, IFN-γ, and STAT3) were detected in CD4+ T cells of healthy controls and psoriatic patients by quantitative real-time PCR (qRT-PCR). In vitro, transfection of miR-125a-5p mimics was used to analyze the effect of miR-125a-5p on the differentiation of Th17 cells by flow cytometry. Imiquimod (IMQ)-induced mouse model was used to evaluate the role of upregulating miR-125a-5p by intradermal injection of agomir-125a-5p in vivo.

Results: miR-125a-5p was downregulated in peripheral blood CD4+ T cells of psoriatic patients, which was positively associated with the proportion of regulatory T cells (Tregs) and negatively correlated with the Psoriasis Area and Severity Index (PASI) score. Moreover, the miR-125a-5p mimics promoted the differentiation of Tregs and downregulated the messenger RNA (mRNA) levels of ETS-1, IFN-γ, and STAT3 in murine CD4+ T cells. Furthermore, agomir-125a-5p alleviated psoriasis-like inflammation in an IMQ-induced mouse model by downregulating the proportion of Th17 cells.

Conclusions: miR-125a-5p may have therapeutic potential in psoriasis by restoring the suppressive function of Tregs on Th17 cells through targeting STAT3, and on Th1 cells indirectly through targeting ETS-1 and IFN-γ.

Keywords: ETS-1; Psoriasis; STAT3; Th17; Tregs; miR125a-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Humans
  • Imiquimod / adverse effects
  • Mice
  • MicroRNAs* / genetics
  • Psoriasis* / genetics
  • STAT3 Transcription Factor / metabolism
  • T-Lymphocytes, Regulatory
  • Th17 Cells

Substances

  • MicroRNAs
  • Imiquimod
  • STAT3 protein, human
  • STAT3 Transcription Factor