气候变化领域集成服务门户(CCPortal): Acetylcholine ameliorates colitis by promoting IL-10 secretion of monocytic myeloid-derived suppressor cells through the nAChR/ERK pathway

CCPortal

DOI	10.1073/pnas.2017762118
	Acetylcholine ameliorates colitis by promoting IL-10 secretion of monocytic myeloid-derived suppressor cells through the nAChR/ERK pathway
	Zheng W.; Song H.; Luo Z.; Wu H.; Chen L.; Wang Y.; Cui H.; Zhang Y.; Wang B.; Li W.; Liu Y.; Zhang J.; Chu Y.; Luo F.; Liu J.
发表日期	2021
ISSN	00278424
卷号	118 期号:11
英文摘要	The alteration of the enteric nervous system (ENS) and its role in neuroimmune modulation remain obscure in the pathogenesis of inflammatory bowel diseases (IBDs). Here, by using the xCell tool and the latest immunolabeling-enabled three-dimensional (3D) imaging of solvent-cleared organs technique, we found severe pathological damage of the entire ENS and decreased expression of choline acetyltransferase (ChAT) in IBD patients. As a result, acetylcholine (ACh), a major neurotransmitter of the nervous system synthesized by ChAT, was greatly reduced in colon tissues of both IBD patients and colitis mice. Importantly, administration of ACh via enema remarkably ameliorated colitis, which was proved to be directly dependent on monocytic myeloid-derived suppressor cells (M-MDSCs). Furthermore, ACh was demonstrated to promote interleukin-10 secretion of M-MDSCs and suppress the inflammation through activating the nAChR/ERK pathway. The present data reveal that the cholinergic signaling pathway in the ENS is impaired during colitis and uncover an ACh-MDSCs neuroimmune regulatory pathway, which may offer promising therapeutic strategies for IBDs. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	ACh; IBD; IL-10; M-MDSCs; NAChR/ERK
语种	英语
scopus关键词	acetylcholine; choline acetyltransferase; enema; interleukin 10; mitogen activated protein kinase; animal cell; animal experiment; animal model; animal tissue; antibody labeling; Article; colitis; colon tissue; controlled study; cytokine release; down regulation; enrichment culture; enteritis; enzyme activity; female; human; human cell; human tissue; inflammatory bowel disease; intestine innervation; mouse; myeloid-derived suppressor cell; nonhuman; priority journal; protein expression; protein synthesis; signal transduction; three-dimensional imaging; ulcerative colitis
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180243
作者单位	Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China; Biotherapy Research Center of Fudan University, Shanghai Engineering Technology Research Center of Intelligent Cancer Medicine, Shanghai, 200032, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China; Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China; Fosun Lead (Shanghai) Healthcare Technologies Co., Ltd., Shanghai, 200437, China; Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China; Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism & Integrative Biology, Fudan University, Shanghai, 200433, China
推荐引用方式 GB/T 7714	Zheng W.,Song H.,Luo Z.,et al. Acetylcholine ameliorates colitis by promoting IL-10 secretion of monocytic myeloid-derived suppressor cells through the nAChR/ERK pathway[J],2021,118(11).
APA	Zheng W..,Song H..,Luo Z..,Wu H..,Chen L..,...&Liu J..(2021).Acetylcholine ameliorates colitis by promoting IL-10 secretion of monocytic myeloid-derived suppressor cells through the nAChR/ERK pathway.Proceedings of the National Academy of Sciences of the United States of America,118(11).
MLA	Zheng W.,et al."Acetylcholine ameliorates colitis by promoting IL-10 secretion of monocytic myeloid-derived suppressor cells through the nAChR/ERK pathway".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021).