Exogenous Hydrogen Peroxide Induces Lipid Raft-Mediated STAT-6 Activation in T Cells

Hee Ja Kim, Jiwoo Lim, Young Soon Jang, Eui Cheol Shin, Hyung Ran Kim, Ju Young Seoh, Ji Soo Lee, Soon Nam Lee, Jihee Lee Kang, Youn Hee Choi

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background/Aims: CD4+ T cells are a critical component of the adaptive immune response. While the mechanisms controlling the differentiation of the Th1, Th17, and regulatory T cell subsets from naïve CD4+ T cells are well described, the factors that induce Th2 differentiation are still largely unknown. Methods: The effects of treatment with exogenous H 2 O 2 on STAT-6 phosphorylation and activation in T cells were examined by immunoblotting, immunofluorescence and gel shift assay. Anti-CD3 antibody and methyl-β-cyclodextrin were utilized to induce lipid raft assembly and to investigate the involvement of lipid rafts, respectively. Results: Jurkat and EL-4 T cells that were exposed to H 2 O 2 showed rapid and strong STAT-6 phosphorylation, and the extent of STAT-6 phosphorylation was enhanced by co-treatment with anti-CD3 antibody. The effect of H 2 O 2 on STAT-6 phosphorylation and translocation was inhibited by disruption of lipid rafts. STAT-6 activation in response to H 2 O 2 treatment regulated IL-4 gene expression, and this response was strengthened by treatment with anti-CD3. Conclusion: Our results indicate that reactive oxygen species such as H 2 O 2 can act on upstream and initiating factors for activation of STAT-6 in T cells and contribute to formation of a positive feedback loop between STAT-6 and IL-4 in the Th2 differentiation process.

Original languageEnglish
Pages (from-to)2467-2480
Number of pages14
JournalCellular Physiology and Biochemistry
Volume42
Issue number6
DOIs
StatePublished - 1 Oct 2017

Keywords

  • IL-4
  • Lipid rafts
  • Reactive oxygen species (ROS)
  • STAT-6
  • Th2 cells

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