Increased expression of miR-338-3p impairs Treg-mediated immunosuppression in pemphigus vulgaris by targeting RUNX1.
Case-Control Studies
Computational Biology
Core Binding Factor Alpha 2 Subunit
/ blood
Databases, Genetic
Forkhead Transcription Factors
/ blood
Glucocorticoids
/ therapeutic use
Humans
Immune Tolerance
/ genetics
MicroRNAs
/ blood
Pemphigus
/ blood
Severity of Illness Index
T-Lymphocytes, Regulatory
/ immunology
Transfection
biomarker
immunosuppression
miRNA
pemphigus vulgaris
regulatory T cell
Journal
Experimental dermatology
ISSN: 1600-0625
Titre abrégé: Exp Dermatol
Pays: Denmark
ID NLM: 9301549
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
revised:
04
04
2020
received:
28
11
2019
accepted:
04
05
2020
pubmed:
10
5
2020
medline:
16
2
2022
entrez:
10
5
2020
Statut:
ppublish
Résumé
Pemphigus vulgaris (PV) is a regulatory T cell (Treg)-associated autoimmune disease. Treg cells maintain immunosuppression by expressing the signature transcription factor FOXP3. MicroRNAs (miRNAs) have frequently emerged as regulators in Treg-mediated immunosuppression. We previously found that miR-338-3p was overexpressed in the peripheral blood mononuclear cells of patients with PV. Herein, we explored the role of miR-338-3p in Treg-mediated immunosuppression by quantitative real-time polymerase chain reaction, analysis of public microarray data, miRNA transfection, Western blotting, flow cytometry, and luciferase reporter assays. Increased expression of miR-338-3p was detected in CD4+ T cells of active PV patients compared with those in healthy controls. Moreover, the miR-338-3p level was positively related to disease severity. Bioinformatics prediction revealed that Runt-related transcription factor 1 (RUNX1), a gene activating FOXP3 expression, was a putative target of miR-338-3p. There was a reduction of FOXP3 and RUNX1 expression in the CD4+ T cells of patients with PV, along with significant correlations with the level of miR-338-3p. MiRNA transfection, mRNA and protein analysis, and luciferase reporter assays verified that miR-338-3p attenuated FOXP3 expression by targeting RUNX1. This study suggests that excessive expression of miR-338-3p attenuates the expression of FOXP3 by targeting RUNX1, contributing to Treg dysfunction in PV.
Substances chimiques
Core Binding Factor Alpha 2 Subunit
0
FOXP3 protein, human
0
Forkhead Transcription Factors
0
Glucocorticoids
0
MIRN338 microRNA, human
0
MicroRNAs
0
RUNX1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
623-629Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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