机构：[1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan Province,China四川大学华西医院[2]West China Biobanks, Department of Clinical Research Management and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University,Chengdu, Sichuan Province, China四川大学华西医院[3]Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China四川大学华西医院[4]Department of Gastrointestinal Surgery, WestChina Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan Province, China[5]Department of Cellular and Molecular Physiology, Institute ofTranslational Medicine, University of Liverpool, Liverpool, Merseyside, UK
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.
基金：
National Natural Science Foundation of China Programme grant
(No. 81772939) and the National Key R&D Programme of China grant (No.
2017YFA0105702) and the National Key R&D Programme of China
(2016YFC1201700) and the Fundamental Research Funds for the Central Universities (2017SCU12033) and the Special Foundation of China Postdoctoral Science
(2018T110980).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|1 区医学
小类|2 区免疫学
最新[2023]版：
大类|2 区医学
小类|2 区免疫学
第一作者：
第一作者机构：[1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan Province,China
通讯作者：
推荐引用方式(GB/T 7714)：
Dai Lei,Liu Yi,Cheng Lin,et al.SARI attenuates colon inflammation by promoting STAT1 degradation in intestinal epithelial cells.[J].Mucosal immunology.2019,12(5):1130-1140.doi:10.1038/s41385-019-0178-9.
APA：
Dai Lei,Liu Yi,Cheng Lin,Wang Huiling,Lin Yi...&Deng Hongxin.(2019).SARI attenuates colon inflammation by promoting STAT1 degradation in intestinal epithelial cells..Mucosal immunology,12,(5)
MLA：
Dai Lei,et al."SARI attenuates colon inflammation by promoting STAT1 degradation in intestinal epithelial cells.".Mucosal immunology 12..5(2019):1130-1140
医学