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

Yan, Kexiang; Zhang, Fuxin; Ren, Jie; Huang, Qiong; Yawalkar, Nikhil; Han, Ling (2023). MicroRNA-125a-5p regulates the effect of Tregs on Th1 and Th17 through targeting ETS-1/STAT3 in psoriasis. Journal of translational medicine, 21(1), p. 678. BioMed Central 10.1186/s12967-023-04427-6

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology

UniBE Contributor:

Yawalkar, Nikhil

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1479-5876

Publisher:

BioMed Central

Language:

English

Submitter:

Pubmed Import

Date Deposited:

02 Oct 2023 14:50

Last Modified:

29 Oct 2023 02:25

Publisher DOI:

10.1186/s12967-023-04427-6

PubMed ID:

37773129

Uncontrolled Keywords:

ETS-1 Psoriasis STAT3 Th17 Tregs miR125a-5p

BORIS DOI:

10.48350/186824

URI:

https://boris.unibe.ch/id/eprint/186824

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