| Literature DB >> 35303419 |
Yikun Yao1, Girak Kim2, Samantha Shafer1, Zuojia Chen2, Satoshi Kubo1, Yanlong Ji3, Jialie Luo2, Weiming Yang4, Sebastian P Perner5, Chrysi Kanellopoulou1, Ann Y Park1, Ping Jiang1, Jian Li2, Safa Baris6, Elif Karakoc Aydiner6, Deniz Ertem7, Daniel J Mulder8, Neil Warner9, Anne M Griffiths9, Chani Topf-Olivestone10, Michal Kori10, Lael Werner11, Jodie Ouahed12, Michael Field12, Chengyu Liu13, Benjamin Schwarz14, Catharine M Bosio14, Sundar Ganesan15, Jian Song16, Henning Urlaub17, Thomas Oellerich18, Stacy A Malaker19, Lixin Zheng1, Carolyn R Bertozzi20, Yu Zhang21, Helen Matthews21, Will Montgomery22, Han-Yu Shih22, Jiansheng Jiang23, Marcus Jones24, Aris Baras24, Alan Shuldiner24, Claudia Gonzaga-Jauregui25, Scott B Snapper12, Aleixo M Muise26, Dror S Shouval11, Ahmet Ozen27, Kuan-Ting Pan5, Chuan Wu28, Michael J Lenardo29.
Abstract
Intestinal mucus forms the first line of defense against bacterial invasion while providing nutrition to support microbial symbiosis. How the host controls mucus barrier integrity and commensalism is unclear. We show that terminal sialylation of glycans on intestinal mucus by ST6GALNAC1 (ST6), the dominant sialyltransferase specifically expressed in goblet cells and induced by microbial pathogen-associated molecular patterns, is essential for mucus integrity and protecting against excessive bacterial proteolytic degradation. Glycoproteomic profiling and biochemical analysis of ST6 mutations identified in patients show that decreased sialylation causes defective mucus proteins and congenital inflammatory bowel disease (IBD). Mice harboring a patient ST6 mutation have compromised mucus barriers, dysbiosis, and susceptibility to intestinal inflammation. Based on our understanding of the ST6 regulatory network, we show that treatment with sialylated mucin or a Foxo3 inhibitor can ameliorate IBD.Entities:
Keywords: ST6GalNAc1; dysbiosis; glycobiology; human genetic disease; inflammatory bowel disease; intestinal homeostasis; intestinal stem cells; mucus barrier; short-chain fatty acids; sialylation
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Year: 2022 PMID： 35303419 PMCID： PMC9088855 DOI： 10.1016/j.cell.2022.02.013
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850