Prolyl hydroxylase 3 (PHD3) expression augments the development of regulatory T cells

被引:12
|
作者
Singh, Yogesh [1 ,2 ,3 ]
Shi, Xiaolong [1 ,2 ,3 ]
Zhang, Shaqiu [1 ,2 ,3 ,4 ]
Umbach, Anja T. [1 ,2 ,3 ]
Chen, Hong [1 ,2 ,3 ]
Salker, Madhuri S. [1 ,2 ,3 ]
Lang, Florian [1 ,2 ,3 ]
机构
[1] Univ Tubingen, Dept Cardiol, Gmelinstr 5, D-72076 Tubingen, Germany
[2] Univ Tubingen, Dept Vasc Med, Gmelinstr 5, D-72076 Tubingen, Germany
[3] Univ Tubingen, Dept Physiol, Gmelinstr 5, D-72076 Tubingen, Germany
[4] Sichuan Agr Univ, Inst Prevent Vet Med, Chengdu 611130, Sichuan, Peoples R China
关键词
PHD3; DMOG; Th17; Tregs; HIF-1; alpha; NUCLEUS PULPOSUS; TGF-BETA; DIFFERENTIATION; STABILITY; T(H)17;
D O I
10.1016/j.molimm.2016.06.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Regulatory T cells (Tregs) are required for effective immune homeostasis by suppressing harmful immune responses against self-antigens. Transcription factor Foxp3 is required for the development of these cells. How Foxp3 is stabilised and affects Tregs development is still incompletely understood. Previous studies have suggested that hypoxia inducible factor gene HIF-1 alpha negatively influences the development of Tregs and enhances the development of IL-17 producing Th17 cells. In this study, we reveal that prolyl hydroxylase 3 (PHD3), which is a negative regulator of HIF-1 alpha, is upregulated in Tregs and enhances the development of Tregs. The PHD3 inhibitor dimethyl oxalylglycine (DMOG) or siRNAs-PHD3, which upregulates HIF-1 alpha, dow -regulated Foxp3 expression, and enhanced the development of Th17 cells. Our observations disclose a novel role of PHD3 in the development of Tregs. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:7 / 12
页数:6
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