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MiR-23a-3p-regulated abnormal acetylation of FOXP3 induces regulatory T cell function defect in Graves’ disease

  • Danhua Zhang , Xinguang Qiu , Jianhua Li , Shouhua Zheng , Liwen Li and Hongchao Zhao EMAIL logo
Published/Copyright: December 3, 2018
Biological Chemistry
From the journal Biological Chemistry Volume 400 Issue 5

Abstract

This study aims to investigate the mechanism of miR-23a-3p in regulating Treg dysfunction in Graves’ disease (GD). The percentage of Treg cells and interleukin (IL)-17+ T cells were determined by flow cytometry. The expression of forkhead box P3 (FOXP3), sirtuin 1 (SIRT1), RAR-related orphan receptor gamma t (RORγt) and miR-23a-3p was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or Western blot. CD4+ T cells were treated with SIRT1 specific inhibitor EX-527 or left untreated. MiR-23a-3p mimic or inhibitor were transfected into CD4+ T cells. Acetylation expression of FOXP3 was analyzed by immunoprecipitation. The suppressive function of Treg was analyzed by the carboxyfluorescein succinimidyl ester (CFSE) assay. The results showed that GD patients have significantly less Treg cells and more IL-17+ T cells. FOXP3 and miR-23a-3p were significantly down-regulated meanwhile SIRT1 and RORγt were up-regulated in GD patients. FOXP3 acetylation level of the GD group was lower than that of control groups. After EX-527 treatment, the percentage of Treg cells, expression and acetylation level of FOXP3 were significantly increased in the GD group. GD Tregs exhibited weaker suppressive activity, miR-23a-3p mimic suppressed SIRT1 expression and suppressive-activity of Tregs whereas it promoted the expression and acetylation level of FOXP3 in the GD group. Our findings suggest that the Treg function defect in GD patients is mediated by the abnormal acetylation of FOXP3, which is regulated by miR-23a-3p via targeting SIRT1.

Keywords: FOXP3 acetylation; Graves’ disease (GD); miR-23a-3p; Treg function defect

Funding source: National Natural Science Foundation of China

Award Identifier / Grant number: 31602600

Funding statement: This study was supported by grants from National Natural Science Foundation of China (NSFC, Grant No. 31602600).

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Received: 2018-08-12
Accepted: 2018-10-26
Published Online: 2018-12-03
Published in Print: 2019-05-27

©2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hsz-2018-0343
Keywords for this article
FOXP3 acetylation; Graves’ disease (GD); miR-23a-3p; Treg function defect

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Complexity of type IV collagens: from network assembly to function
  4. Structural and mechanistic aspects of S-S bonds in the thioredoxin-like family of proteins
  5. Oxidative stress and antioxidants in the pathophysiology of malignant melanoma
  6. Research Articles/Short Communications
  7. Genes and Nucleic Acids
  8. Dynamic characteristics of the mitochondrial genome in SCNT pigs
  9. Protein Structure and Function
  10. Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1
  11. Molecular Medicine
  12. The comparative biochemistry of viruses and humans: an evolutionary path towards autoimmunity
  13. MiR-23a-3p-regulated abnormal acetylation of FOXP3 induces regulatory T cell function defect in Graves’ disease
  14. Cell Biology and Signaling
  15. Evidence for a protective role of the CX3CL1/CX3CR1 axis in a model of amyotrophic lateral sclerosis
  16. LncRNA TINCR/microRNA-107/CD36 regulates cell proliferation and apoptosis in colorectal cancer via PPAR signaling pathway based on bioinformatics analysis
  17. Regulatory effect of hsa-miR-5590-3P on TGFβ signaling through targeting of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts
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