Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages

被引：66

作者：

Jiang, Xingwei ^{[1
,2
,6
]}

Yu, Jiahui ^{[3
]}

Shi, Qingzhu ^{[1
]}

Xiao, Yan ^{[4
]}

Wang, Wei ^{[1
,3
]}

Chen, Guojiang ^{[1
]}

Zhao, Zhi ^{[5
]}

Wang, Renxi ^{[1
]}

Xiao, He ^{[1
]}

Hou, Chunmei ^{[1
]}

Feng, Jiannan ^{[1
]}

Ma, Yuanfang ^{[3
]}

Shen, Beifen ^{[1
]}

Wang, Lili ^{[2
]}

Li, Yan ^{[1
]}

Han, Gencheng ^{[1
]}

机构：

[1] Beijing Inst Basic Med Sci, Dept Immunol, Beijing 100850, Peoples R China

[2] State Key Lab Toxicol & Med Countermeasure, Beijing 100850, Peoples R China

[3] Henan Univ, Sch Med, Inst Immunol, Kaifeng 475001, Peoples R China

[4] Chinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Dept Resp Dis, Beijing 100037, Peoples R China

[5] YIHE Hosp, Zhengzhou Peoples Hosp, Dept Pathol, Zhengzhou 450000, Peoples R China

[6] Beijing Inst Transfus Med, Beijing 100850, Peoples R China

来源：

CLINICAL IMMUNOLOGY | 2015年 / 160卷 / 02期

基金：

中国国家自然科学基金; 北京市自然科学基金;

关键词：

Tim-3; Macrophages; DSS colitis; Immune homeostasis; INFLAMMATORY-BOWEL-DISEASE; T-CELL IMMUNOGLOBULIN; ULCERATIVE-COLITIS; CROHNS-DISEASE; AUTOIMMUNE INFLAMMATION; IMMUNE-RESPONSES; MICE; ACTIVATION; EXPRESSION; PATHWAY;

D O I：

10.1016/j.clim.2015.07.008

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but the underlying mechanism is unknown. Here, we demonstrated that, in mouse with DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing macrophages with intestinal lymphocytes decreased the pro-inflammatory response. Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim-3 blockade failed to exacerbate colitis or increase M1 macrophage response in the TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR-4 downstream transcriptional factor regulating macrophage polarization. A better understanding of this pathway may shed new light on colitis pathogenesis and result in a new therapeutic strategy. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：328 / 335

页数：8

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