Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation
Open Access
- 16 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-17
- https://doi.org/10.1038/s41467-021-21277-2
Abstract
Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF–dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn’s diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas–intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation.Funding Information
- Japan Agency for Medical Research and Development (20gm6010012h0004, 20gm6210024h0001, 16jm0110012h0002, 18ek0410032h0003)
- MEXT | Japan Society for the Promotion of Science (18H05280, 19H03450, 16H06243, 17K19550, 19K22634, 18KK0432, 18H05280)
This publication has 82 references indexed in Scilit:
- Microbe-dependent CD11b+ IgA+ plasma cells mediate robust early-phase intestinal IgA responses in miceNature Communications, 2013
- Robustness of Gut Microbiota of Healthy Adults in Response to Probiotic Intervention Revealed by High-Throughput PyrosequencingDNA Research, 2013
- Mucosa-associated but not luminal Escherichia coli is augmented in Crohn’s disease and ulcerative colitisGut Pathogens, 2012
- Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptorsNature Communications, 2012
- CX3CR1 regulates intestinal macrophage homeostasis, bacterial translocation, and colitogenic Th17 responses in miceJCI Insight, 2011
- Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosisProceedings of the National Academy of Sciences of the United States of America, 2010
- The pancreatic zymogen granule membrane protein, GP2, binds Escherichia colitype 1 FimbriaeBMC Gastroenterology, 2009
- The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteriaProceedings of the National Academy of Sciences of the United States of America, 2008
- Rap1 Activation Plays a Regulatory Role in Pancreatic Amylase SecretionOnline Journal of Public Health Informatics, 2008
- The class V myosin motor, myosin 5c, localizes to mature secretory vesicles and facilitates exocytosis in lacrimal aciniAmerican Journal of Physiology-Cell Physiology, 2008