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The role of granulocytes in maintaining epithelial-stem cell driven intestinal homeostasis

ReferenceBBS/E/F/00044450
Principal Investigator / Supervisor Dr Anastasia Sobolewski
Co-Investigators /
Co-Supervisors
Institution Quadram Institute Bioscience
DepartmentQuadram Institute Bioscience Department
Funding typeResearch
Value (£) 1,275,326
StatusCompleted
TypeInstitute Project
Start date 01/04/2010
End date 31/12/2015
Duration68 months

Abstract

The intestinal epithelium forms a vital physical barrier to prevent bacteria and luminal antigens from interacting with mucosal immune cells. Barrier function is maintained by stem cell-driven tissue renewal and regeneration in response to injury/infection. Epithelial recognition of bacterial products occurs under steady-state conditions and plays an important role in the maintenance of intestinal epithelial homeostasis. Bacteria have been shown to regulate epithelial stem cell biology through direct and indirect mechanisms in lower organisms such as drosophila, but whether this occurs in mammalian systems remains to be elucidated. Mobilisation of tissue-resident immune cells to the stem cell niche is also a likely mechanism by which luminal bacteria regulate stem cell-driven epithelial. Granulocytes play an important role in tissue homeostasis in a variety of tissues as well as being implicated in epithelial repair/regeneration and resolution of inflammation in IBD. However, it is not clear how signals and dynamic interactions between bacteria, granulocytes and the epithelium work in concert to orchestrate epithelial stem cell-driven tissue renewal. Objective: to determine the role granulocytes play in communicating commensal luminal inputs to epithelial stem cells? We use real-time confocal bioimaging of the mouse intestinal stem cell niche (Lgr5-EGFP transgenic mice), intestinal epithelial crypts, granulocytes and fluorescent E.coli to determine their role in epithelial stem cell-driven tissue homeostasis. The outcome of this study is fundamental to the understanding of the role of granulocytes and commensal microbes in tissue homeostasis, regeneration and even inflammation.

Summary

unavailable
Committee Not funded via Committee
Research TopicsImmunology, Microbiology, Stem Cells
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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