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

页码：3381 / 3398

页数：18

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