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Mucin glycans as novel immunoregulators of host response

Reference	BBS/E/F/00044504
Principal Investigator / Supervisor	Professor Nathalie Juge
Co-Investigators / Co-Supervisors	Dr Norihito Kawasaki
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	100,148
Status	Completed
Type	Institute Project
Start date	09/02/2015
End date	31/03/2016
Duration	13 months

Abstract

This project investigates the molecular mechanisms underlying a novel role of mucins as immunoregulators of gut homeostasis. Mucins are heavily glycosylated proteins covering the gastrointestinal epithelium, providing a physical and biological barrier function against harmful molecules while maintaining a homeostatic relationship with our gut microbiota. In addition to this protective function, secreted mucins were recently shown to implement a biological signaling to suppress excessive host immune response whereby mucins bind to dendritic cells (DCs), a key regulator for the gut immune system, thus inhibiting cellular activation. This immunosuppressive effect was proposed to be mediated in vivo by two carbohydrate-binding proteins, Galectin-3 and/or Dectin-1, expressed on DCs, although direct evidence of binding remains to be determined. This project addresses the specificity and implication of mucin glycan-DC interactions at the molecular level by combining expertise from the Juge’s Lab in gut mucin biology and Kawasaki’s Lab in gut immunology, both having common interest and complementary expertise in carbohydrate-lectin interactions. We will characterize mucin-lectin interaction at the molecular level using atomic force microscopy and reporter cell-based assays and determine the immune response of human or mouse DCs in response to mucin treatment. Several outputs such as cytokine production and proliferation will be assessed by ELISA and flow cytometry. We will then investigate the carbohydrate structures on mucins responsible for the reported immunosuppressive effect by using mucins of different glycosylation signatures following a chemo-enzymatic approach. Since mucin glycosylation is altered in inflammation and cancer, defining the precise mucin glycan structures recognised by mammalian lectins to elicit a tolerogenic response is critical to understand the role of these interactions in health and disease.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Diet and Health, Immunology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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