中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海营养与健康研究所
  3. 中国科学院上海生命科学研究院营养科学研究所
Macrophage/microglial Ezh2 facilitates autoimmune inflammation through inhibition of Socs3

文献类型：期刊论文

作者Zhang, Xingli1; Wang, Yan1; Yuan, Jia1; Pei, Siyu1; Xu, Jing1; Liu, Junli1; Yu, Tao1; Gan, Shucheng1; Qiu, Ju1; Xiao, Yichuan1
刊名JOURNAL OF EXPERIMENTAL MEDICINE
出版日期2018
卷号215期号:5页码:1365-1382
ISSN号0022-1007
DOI10.1084/jem.20171417
文献子类Article
英文摘要Histone 3 Lys27 (H3K27) trimethyltransferase Ezh2 is implicated in the pathogenesis of autoimmune inflammation. Nevertheless, the role of Ezh2 in macrophage/microglial activation remains to be defined. In this study, we identified that macrophage/microglial H3K27me3 or Ezh2, rather than functioning as a repressor, mediates toll-like receptor (TLR)-induced proinflammatory gene expression, and therefore Ezh2 depletion diminishes macrophage/microglial activation and attenuates the autoimmune inflammation in dextran sulfate sodium-induced colitis and experimental autoimmune encephalomyelitis. Mechanistic characterizations indicated that Ezh2 deficiency directly stimulates suppressor of cytokine signaling 3 (Socs3) expression and therefore enhances the Lys48-linked ubiquitination and degradation of tumor necrosis factor receptor-associated factor 6. As a consequence, TLR-induced MyD88-dependent nuclear factor.B activation and the expression of proinflammatory genes in macrophages/microglia are compromised in the absence of Ezh2. The functional dependence of Ezh2 for Socs3 is further illustrated by the rescue experiments in which silencing of Socs3 restores macrophage activation and rescues autoimmune inflammation in macrophage/microglial Ezh2-deficient mice. Together, these findings establish Ezh2 as a macrophage lineage-specific mediator of autoimmune inflammation and highlight a previously unknown mechanism of Ezh2 function.
学科主题Immunology ; Research & Experimental Medicine
WOS关键词ANTIGEN-PRESENTING CELLS ; MULTIPLE-SCLEROSIS ; MACROPHAGE POLARIZATION ; METHYLTRANSFERASE EZH2 ; INNATE IMMUNITY ; T-CELLS ; MICROGLIA ; MONOCYTES ; DISEASE ; POLYCOMB
语种英语
出版者ROCKEFELLER UNIV PRESS
WOS记录号WOS:000440819800010
版本出版稿
源URL[http://202.127.25.144/handle/331004/1029]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol,Inst Hlth Sci, Shanghai, Peoples R China;
2.Univ Chinese Acad Sci, Key Lab Stem Cell Biol, Chinese Acad Sci, Ctr Excellence Mol Cell Sci,Inst Hlth Sci,Shangha, Shanghai, Peoples R China;
3.Jiangsu Univ, Affiliated Hosp, Dept Nucl Med, Zhenjiang, Peoples R China;
4.Xinxiang Med Univ, Sch Lab Med, Xinxiang, Peoples R China;
5.Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing, Peoples R China;
6.Univ Verona, Sect Gen Pathol, Dept Med, Verona, Italy;
7.Zhejiang Univ, Life Sci Inst, Hangzhou, Zhejiang, Peoples R China,
推荐引用方式
GB/T 7714		 Zhang, Xingli,Wang, Yan,Yuan, Jia,et al. Macrophage/microglial Ezh2 facilitates autoimmune inflammation through inhibition of Socs3[J]. JOURNAL OF EXPERIMENTAL MEDICINE,2018,215(5):1365-1382.
APA Zhang, Xingli.,Wang, Yan.,Yuan, Jia.,Pei, Siyu.,Xu, Jing.,...&,.(2018).Macrophage/microglial Ezh2 facilitates autoimmune inflammation through inhibition of Socs3.JOURNAL OF EXPERIMENTAL MEDICINE,215(5),1365-1382.
MLA Zhang, Xingli,et al."Macrophage/microglial Ezh2 facilitates autoimmune inflammation through inhibition of Socs3".JOURNAL OF EXPERIMENTAL MEDICINE 215.5(2018):1365-1382.

入库方式： OAI收割

来源：上海营养与健康研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。