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Publication : Mucus sialylation determines intestinal host-commensal homeostasis.

First Author  Yao Y Year  2022
Journal  Cell Volume  185
Issue  7 Pages  1172-1188.e28
PubMed ID  35303419 Mgi Jnum  J:324883
Mgi Id  MGI:7259978 Doi  10.1016/j.cell.2022.02.013
Citation  Yao Y, et al. (2022) Mucus sialylation determines intestinal host-commensal homeostasis. Cell 185(7):1172-1188.e28
abstractText  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.
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