T helper 17 (Th17) cells are a CD4⁺ T cell subset that produces IL-17A to mediate inflammation and autoimmunity. IL-2 inhibits Th17 cell differentiation. However, the mechanism by which IL-2 is suppressed during Th17 cell differentiation remains unclear. Here, we show that phosphatase and tensin homologue (PTEN) is a key factor that regulates Th17 cell differentiation by suppressing IL-2 production. Th17-specific Pten deletion (Pten^fl/flIl17a^cre) impairs Th17 cell differentiation in vitro and ameliorated symptoms of experimental autoimmune encephalomyelitis (EAE), a model of Th17-mediated autoimmune disease. Mechanistically, Pten deficiency up-regulates IL-2 and phosphorylation of STAT5, but reduces STAT3 phosphorylation, thereby inhibiting Th17 cell differentiation. PTEN inhibitors block Th17 cell differentiation in vitro and in the EAE model. Thus, PTEN plays a key role in Th17 cell differentiation by blocking IL-2 expression.

T辅助细胞17（Th17）细胞是CD4 ⁺ T细胞亚群，可产生IL-17A来介导炎症和自身免疫。IL-2抑制Th17细胞分化。但是，在Th17细胞分化过程中抑制IL-2的机制仍不清楚。在这里，我们表明磷酸酶和张力蛋白同源物（PTEN）是通过抑制IL-2产生来调节Th17细胞分化的关键因素。Th17特异性Pten缺失（Pten ^{fl / fl} Il17a ^cre）在体外损害Th17细胞分化，并改善了实验性自身免疫性脑脊髓炎（EAE）（一种Th17介导的自身免疫性疾病的模型）的症状。机械上，Pten缺乏会上调IL-2和STAT5的磷酸化，但会降低STAT3的磷酸化，从而抑制Th17细胞分化。PTEN抑制剂可在体外和EAE模型中阻断Th17细胞分化。因此，PTEN通过阻断IL-2表达在Th17细胞分化中起关键作用。