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.

由原核生物和真核生物产生的多胺是具有多效作用的生物活性物质。越来越多的证据表明，多胺可通过抑制单核细胞和巨噬细胞中促炎细胞因子的表达来促进抗炎反应。然而，多胺对CD4 ⁺ T细胞反应的影响仍有待阐明。在这里，我们研究了多胺对幼稚CD4 ⁺ T细胞体外细胞命运决定的影响。我们发现内源性产生的多胺对于T辅助2（Th2）细胞的发展至关重要。用多胺生物合成抑制剂DL-2-二氟甲基鸟氨酸（DFMO）处理可减少CD4 ^+中GATA3的表达T2倾斜条件下的T细胞。补充外源多胺可以缓解DFMO处理CD4 ⁺ T细胞引起的GATA3下调。转录组分析显示，即使在Th2倾斜的条件下，内源多胺的剥夺也会导致Th9相关基因（例如Il9，Irf4和Batf3）的表达上调。在Th2和Th9偏斜条件下，细胞内多胺的减少减少GATA3表达，但增加产生IL-9的CD4 ⁺ T细胞。此外，口服DFMO可增加产生IL-9的CD4 ⁺小鼠小肠中的T细胞。因此，我们的数据表明，多胺在调节Th2 / Th9平衡中起关键作用。