PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs

被引：55

作者：

Lee, Seung Hoon ^{[1
]}

Park, Jin-Sil ^{[1
]}

Byun, Jae-Kyung ^{[1
]}

Jhun, JooYeon ^{[1
]}

Jung, KyungAh ^{[2
]}

Seo, Hyeon-Beom ^{[1
]}

Moon, Young-Mee ^{[1
]}

Kim, Ho-Youn ^{[1
,3
]}

Park, Sung-Hwan ^{[1
,3
]}

Cho, Mi-La ^{[1
,4
]}

机构：

[1] Catholic Univ Korea, Catholic Res Inst Med Sci, Rheumatism Res Ctr, Seoul, South Korea

[2] Impact Biotech, Korea 505 Banpo Dong, Seoul 137040, South Korea

[3] Catholic Univ Korea, Sch Med, Div Rheumatol, Dept Internal Med, Seoul, South Korea

[4] Catholic Univ Korea, Coll Med, Lab Immune Network, Conversant Res Consortium Immunol Dis, Seoul, South Korea

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; SYNOVIAL FIBROBLASTS; IL-17; PRODUCTION; NECROSIS-FACTOR; CELLS; INFLAMMATION; CYTOKINES; MODEL; EXPRESSION;

D O I：

10.1038/srep34617

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3 activation. Recently, inactivation of STAT3 has been demonstrated as a therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation. Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation. Systemic infusion of PTEN overexpression downregulated CIA severity. In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells. We observed that PTEN expression downregulated by p53 deficiency induced the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and dysregulated the population of Th17 and Treg. These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy.

引用

页数：11

共 49 条

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