Award details

Immune responses to the environment

Reference	BBS/E/B/000C0407
Principal Investigator / Supervisor	Dr Martin Turner
Co-Investigators / Co-Supervisors	Dr Geoff Butcher, Professor Klaus Okkenhaug, Dr Marc Veldhoen
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	3,913,356
Status	Completed
Type	Institute Project
Start date	01/04/2012
End date	31/03/2017
Duration	59 months

Abstract

The presence of microbial populations in the gut lumen presents a delicate problem for the immune system. It must maintain tolerance against food antigens and bacteria required for normal physiology while simultaneously neutralising pathogenic microorganisms. The recognition and appropriate response to commensal and pathogenic micro-organisms by the immune system must be maintained throughout the life-course [62]. The intestine contains highly organized lymphoid tissues, such as lymph nodes and the gutassociated lymphoid tissue (GALT). The latter consists of specialised structures such as Peyer's Patches, cryptopatches, and hundreds of isolated follicles located in the outer connective tissue called the lamina propria (LP). In addition, a population of intra-epithelial lymphocytes (IELs), consisting of TCRƒaß?CD8aa? and TCR?d? T cells, resides beneath the single-cell epithelial barrier. The proximity of IELs ensures frequent interactions with intestinal epithelial cells (IECs). Such epithelial-immune integration is to be distinguished from infiltration of the epithelia by systemic immune cells in response to inflammatory cues. However, IELs are positioned to be amongst the first cells to sense and respond to changes in the environment. We will examine the biology of IELs, their interaction with the epithelial barrier and the repertoire of gut bacteria. To date, few molecules and processes have been described that mediate host-microbiota associations [63]. Many genes, molecules, pathways and regulatory principles that are used for the development and homeostasis of lymphocytes are re-used during the activation of these cells as part of the response to infection. This important principle has been demonstrated using mouse models in which genes are deleted at specific developmental stages. We will examine the roles of genes and pathways that are important for lymphocyte development and homeostasis for their contribution to immunity and the integrated function of different organ systems. Our ISP will continue its studies of the regulation of antibody responses and T cell activation, focusing on signalling pathways and taking advantage of the new small animal facilities to perform immune challenges.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Immunology, Microbiology
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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