Polyamines polarized Th2/Th9 cell-fate decision by regulating GATA3 expression

Atsuo Nakamura, Daisuke Takahashi, Yutaka Nakamura, Takahiro Yamada, Mitsuharu Matsumoto, Koji Hase

Research output: Contribution to journalArticle

Abstract

Polyamines produced by both prokaryotes and eukaryotes are bioactive substances with pleiotropic effects. Accumulating evidence has demonstrated that polyamines contribute to anti-inflammatory responses by suppressing the expression of proinflammatory cytokines in mononuclear cells and macrophages. However, the effects of polyamines on CD4+ T cell responses remain to be elucidated. Here, we investigated the effect of polyamines on cell fate decisions of naïve CD4+ T cells in vitro. We found that endogenously generated polyamines are essential for the development of T helper 2 (Th2) cells. Treatment with DL-2-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, diminished GATA3 expression in CD4+ T cells under Th2-skewed conditions. Supplementation of exogenous polyamines rescued GATA3 downregulation caused by DFMO treatment in CD4+ T cells. Transcriptome analysis revealed that deprivation of endogenous polyamines resulted in upregulated Th9-related genes, such as Il9, Irf4, and Batf3, even under the Th2-skewing conditions. Depletion of intracellular polyamines reduced GATA3 expression but increased IL-9-producing CD4+ T cells under both Th2 and Th9-skewing conditions. Furthermore, oral administration of DFMO increased IL-9-producing CD4+ T cells in small intestine in mice. Thus, our data indicate that polyamines play a critical role in the regulation of the Th2/Th9 balance.

Original languageEnglish
Article number108587
JournalArchives of Biochemistry and Biophysics
Volume693
DOIs
Publication statusPublished - 2020 Oct 30

Keywords

  • Differentiation
  • GATA3
  • Polyamines
  • Th2
  • Th9

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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