Kim Hyeong Su, Jang Sung Woong, Lee Wonyong, Kim Kiwan, Sohn Hyogon, Hwang Soo Seok, Lee Gap Ryol
Department of Life Science, Sogang University, Seoul, South Korea.
Department of Life Science, Sogang University, Seoul, South Korea
J Exp Med. 2017 Nov 6;214(11):3381-3398. doi: 10.1084/jem.20170523. Epub 2017 Oct 10.
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 deletion ( ) impairs Th17 cell differentiation in vitro and ameliorated symptoms of experimental autoimmune encephalomyelitis (EAE), a model of Th17-mediated autoimmune disease. Mechanistically, 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.
辅助性T细胞17（Th17细胞）是一种CD4 T细胞亚群，可产生白细胞介素-17A（IL-17A）来介导炎症和自身免疫。白细胞介素-2（IL-2）抑制Th17细胞分化。然而，在Th17细胞分化过程中IL-2被抑制的机制仍不清楚。在此，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细胞分化的关键因子。Th17特异性缺失（ ）在体外损害Th17细胞分化，并改善实验性自身免疫性脑脊髓炎（EAE）的症状，EAE是一种Th17介导的自身免疫性疾病模型。从机制上讲， 缺陷上调IL-2和信号转导子和转录激活子5（STAT5）的磷酸化，但降低信号转导子和转录激活子3（STAT3）的磷酸化，从而抑制Th17细胞分化。PTEN抑制剂在体外和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。
