PTEN drives Th17 cell differentiation by preventing IL-2 production

被引：52
|
作者：
Kim, Hyeong Su [1 ]
Jang, Sung Woong [1 ]
Lee, Wonyong [1 ]
Kim, Kiwan [1 ]
Sohn, Hyogon [1 ]
Hwang, Soo Seok [1 ]
Lee, Gap Ryol [1 ]
机构：
[1] Sogang Univ, Dept Life Sci, Seoul, South Korea
来源：
JOURNAL OF EXPERIMENTAL MEDICINE | 2017年 / 214卷 / 11期
基金：
新加坡国家研究基金会;
关键词：
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INTERLEUKIN-2; GENE-EXPRESSION; IL-17-PRODUCING T-CELLS; NF-KAPPA-B; SIGNALING PATHWAY; TUMOR-SUPPRESSOR; TENSIN HOMOLOG; ROR-GAMMA; LINEAGE DIFFERENTIATION; RHEUMATOID-ARTHRITIS;
D O I：
10.1084/jem.20170523
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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/fl)Il17a(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.
引用
收藏
页码：3381 / 3398
页数：18
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