SARI attenuates colon inflammation by promoting STAT1 degradation in intestinal epithelial cells

被引：20

作者：

Dai, Lei ^{[1
,2
,3
]}

Liu, Yi ^{[1
,2
,3
]}

Cheng, Lin ^{[1
,2
,3
]}

Wang, Huiling ^{[1
,2
,3
]}

Lin, Yi ^{[1
,2
,3
]}

Shi, Gang ^{[1
,2
,3
]}

Dong, Zhexu ^{[1
,2
,3
]}

Li, Junshu ^{[1
,2
,3
]}

Fan, Ping ^{[4
,5
]}

Wang, Qinnan ^{[1
,2
,3
]}

Su, Xiaolan ^{[1
,2
,3
]}

Zhang, Shuang ^{[2
]}

Yang, Yang ^{[1
,2
,3
]}

Hu, Xun ^{[4
,5
]}

Huang, Wei ^{[4
,5
]}

Zhou, Zongguang ^{[6
,7
]}

Yu, Dechao ^{[1
,2
,3
]}

Probert, Christopher ^{[8
]}

Wei, Yuquan ^{[1
,2
,3
]}

Deng, Hongxin ^{[1
,2
,3
]}

机构：

[1] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu, Sichuan, Peoples R China

[2] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu, Sichuan, Peoples R China

[3] Collaborat Innovat Ctr Biotherapy, Chengdu, Sichuan, Peoples R China

[4] Sichuan Univ, West China Hosp, Dept Clin Res Management, West China Biobanks, Chengdu, Sichuan, Peoples R China

[5] Sichuan Univ, West China Hosp, West China Liverpool Biomed Res Ctr, Chengdu, Sichuan, Peoples R China

[6] Sichuan Univ, West China Hosp, Dept Gastrointestinal Surg, Chengdu, Sichuan, Peoples R China

[7] Sichuan Univ, State Key Lab Biotherapy, Chengdu, Sichuan, Peoples R China

[8] Univ Liverpool, Inst Translat Med, Dept Cellular & Mol Physiol, Liverpool, Merseyside, England

来源：

MUCOSAL IMMUNOLOGY | 2019年 / 12卷 / 05期

基金：

中国国家自然科学基金;

关键词：

UP-REGULATION; IFN-GAMMA; CANCER; EXPRESSION; COLITIS; RECRUITMENT; MACROPHAGES; RESPONSES; IMMUNITY; PROGRESSION;

D O I：

10.1038/s41385-019-0178-9

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

SARI functions as a suppressor of colon cancer and predicts survival of colon cancer patients, but its role in regulating colitis has not been characterized. Here we show that SARI(-/- )mice were highly susceptible to colitis, which was associated with enhanced macrophage infiltration and inflammatory cytokine production. Bone marrow reconstitution experiments demonstrated that disease susceptibility was not dependent on the deficiency of SARI in the immune compartment but on the protective role of SARI in the intestinal epithelial cells (IECs). Furthermore, SARI deficiency enhanced Chemokine (C-C motif) Ligand 2 (CCL2) production and knockout of CCR2 blocks the promoting role of SARI deficiency on colitis. Mechanistically, SARI directly targets and promotes signal transducer and activator of transcription 1 (STAT1) degradation in IECs, followed by persistent inactivation of the STAT1/CCL2 transcription complex. In summary, SARI attenuated colitis in mice by impairing colitis-dependent STAT1/CCL2 transcriptional activation in IECs and macrophages recruitment in colon tissue.

引用

页码：1130 / 1140

页数：11

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