Skip to main content

miR-17-92 cluster targets phosphatase and tensin homology and Ikaros Family Zinc Finger 4 to promote TH17-mediated inflammation.

Publication ,  Journal Article
Liu, S-Q; Jiang, S; Li, C; Zhang, B; Li, Q-J
Published in: J Biol Chem
May 2, 2014

The miR-17-92 cluster regulates a broad spectrum of biological processes of T cell immunity. This cluster was found to facilitate T cell proliferation, enhance antitumor activities and promote T cell-dependent antibody responses. However, little is known about the role of this miRNA cluster in the development of autoimmune diseases. Multiple sclerosis is a neuro-destructive autoimmune disease caused by the pathogenicity of TH17 cells, whose differentiation is tightly controlled by a variety of transcriptional and post-transcriptional regulators. Our study unveils the critical role of miR-17-92 in TH17 differentiation: T cell-specific miR-17-92 deficiency reduced TH17 differentiation and ameliorated experimental autoimmune encephalomyelitis (EAE) symptoms. We demonstrated that miR-17 and miR-19b are the two miRNAs in this cluster responsible for promoting TH17 responses. MiR-19b represses the expression of Phosphatase and Tensin Homology (PTEN), thereby augmenting the PI3K-AKT-mTOR axis essential for proper TH17 differentiation. Meanwhile, miR-17 enhances TH17 polarization by inhibiting a novel target, Ikaros Family Zinc Finger 4 (IKZF4). By establishing the miR-17-92 cluster as a key driver of TH17 responses, our data identify this miRNA cluster as a potential therapeutic target for the clinical intervention of multiple sclerosis.

Duke Scholars

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

May 2, 2014

Volume

289

Issue

18

Start / End Page

12446 / 12456

Location

United States

Related Subject Headings

  • Th17 Cells
  • Reverse Transcriptase Polymerase Chain Reaction
  • PTEN Phosphohydrolase
  • Nerve Tissue Proteins
  • Multiple Sclerosis
  • Multigene Family
  • MicroRNAs
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, S.-Q., Jiang, S., Li, C., Zhang, B., & Li, Q.-J. (2014). miR-17-92 cluster targets phosphatase and tensin homology and Ikaros Family Zinc Finger 4 to promote TH17-mediated inflammation. J Biol Chem, 289(18), 12446–12456. https://doi.org/10.1074/jbc.M114.550723
Liu, Si-Qi, Shan Jiang, Chaoran Li, Baojun Zhang, and Qi-Jing Li. “miR-17-92 cluster targets phosphatase and tensin homology and Ikaros Family Zinc Finger 4 to promote TH17-mediated inflammation.J Biol Chem 289, no. 18 (May 2, 2014): 12446–56. https://doi.org/10.1074/jbc.M114.550723.
Liu, Si-Qi, et al. “miR-17-92 cluster targets phosphatase and tensin homology and Ikaros Family Zinc Finger 4 to promote TH17-mediated inflammation.J Biol Chem, vol. 289, no. 18, May 2014, pp. 12446–56. Pubmed, doi:10.1074/jbc.M114.550723.
Liu S-Q, Jiang S, Li C, Zhang B, Li Q-J. miR-17-92 cluster targets phosphatase and tensin homology and Ikaros Family Zinc Finger 4 to promote TH17-mediated inflammation. J Biol Chem. 2014 May 2;289(18):12446–12456.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

May 2, 2014

Volume

289

Issue

18

Start / End Page

12446 / 12456

Location

United States

Related Subject Headings

  • Th17 Cells
  • Reverse Transcriptase Polymerase Chain Reaction
  • PTEN Phosphohydrolase
  • Nerve Tissue Proteins
  • Multiple Sclerosis
  • Multigene Family
  • MicroRNAs
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice