Polyamines polarized Th2/Th9 cell-fate decision by regulating GATA3 expression.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS(2020)
摘要
Polyamines produced by both prokaryotes and eukaryotes are bioactive substances with pleiotmpic 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 naive 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.
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关键词
Th2,Th9,Differentiation,GATA3,Polyamines
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