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学科主题口腔医学
Hydrogen Sulfide Promotes Tet1-and Tet2-Mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis
Yang, Ruili1,2,3; Qu, Cunye3; Zhou, Yu4; Konkel, Joanne E.5; Shi, Shihong3; Liu, Yi6,7; Chen, Chider2,3; Liu, Shiyu3; Liu, Dawei1; Chen, Yibu8; Zandi, Ebrahim4; Chen, Wanjun5; Zhou, Yanheng1; Shi, Songtao2,3
刊名IMMUNITY
2015-08-18
DOI10.1016/j.immuni.2015.07.017
43期:2页:251-263
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Immunology
研究领域[WOS]Immunology
关键词[WOS]CYSTATHIONINE-BETA-SYNTHASE ; TRANSCRIPTION FACTOR FOXP3 ; EMBRYONIC STEM-CELLS ; DNA METHYLATION ; GENE-EXPRESSION ; TARGET GENES ; CIS-ELEMENT ; MOUSE MODEL ; TET2 ; 5-HYDROXYMETHYLCYTOSINE
英文摘要

Regulatory T (Treg) cells are essential for maintenance of immune homeostasis. Here we found that hydrogen sulfide (H2S) was required for Foxp3(+) Treg cell differentiation and function and that H2S deficiency led to systemic autoimmune disease. H2S maintained expression of methylcytosine dioxygenases Tet1 and Tet2 by sulfhydrating nuclear transcription factor Y subunit beta (NFYB) to facilitate its binding to Tet1 and Tet2 promoters. Transforming growth factor-beta (TGF-beta)-activated Smad3 and interleukin-2 (IL-2)-activated Stat5 facilitated Tet1 and Tet2 binding to Foxp3. Tet1 and Tet2 catalyzed conversion of 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine (5hmC) in Foxp3 to establish a Treg-cell-specific hypomethylation pattern and stable Foxp3 expression. Consequently, Tet1 and Tet2 deletion led to Foxp3 hypermethylation, impaired Treg cell differentiation and function, and autoimmune disease. Thus, H2S promotes Tet1 and Tet2 expression, which are recruited to Foxp3 by TGF-beta and IL-2 signaling to maintain Foxp3 demethylation and Treg-cell-associated immune homeostasis.

语种英语
WOS记录号WOS:000360101200009
Citation statistics
Cited Times:56[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50912
Collection北京大学口腔医学院_牙周科
北京大学口腔医学院_口腔正畸科
作者单位1.Peking Univ, Sch & Hosp Stomatol, Dept Orthodont, Beijing 100081, Peoples R China
2.Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA
3.Univ So Calif, Ostrow Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA
4.Univ So Calif, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA
5.Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA
6.Capital Med Univ, Sch Stomatol, Lab Tissue Regenerat & Immunol, Beijing 100050, Peoples R China
7.Capital Med Univ, Sch Stomatol, Dept Periodont, Beijing 100050, Peoples R China
8.Univ So Calif, Keck Sch Med, Norris Med Lib, Los Angeles, CA 90033 USA
Recommended Citation
GB/T 7714
Yang, Ruili,Qu, Cunye,Zhou, Yu,et al. Hydrogen Sulfide Promotes Tet1-and Tet2-Mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis[J]. IMMUNITY,2015,43(2):251-263.
APA Yang, Ruili.,Qu, Cunye.,Zhou, Yu.,Konkel, Joanne E..,Shi, Shihong.,...&Shi, Songtao.(2015).Hydrogen Sulfide Promotes Tet1-and Tet2-Mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis.IMMUNITY,43(2),251-263.
MLA Yang, Ruili,et al."Hydrogen Sulfide Promotes Tet1-and Tet2-Mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis".IMMUNITY 43.2(2015):251-263.
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