Defining the impact of inflammatory bowel disease associated SNPs on the immunobiology of human mucosal T lymphocytes (360G-Wellcome-091993_Z_10_Z)

£268,900

AIM: The phenotypic analysis of intestinal T lymphocytes including functional studies of genetic polymorphisms associated with Crohn's disease. Lymphocytes will be extracted from blood and intestinal biopsies from healthy individuals stratified for two key SNPs identified from GWA studies as associated with IBD susceptibility. One SNP is a coding variant in the IL23 receptor, involved in differentiation of T lymphocytes to IL17 production, and one a non-coding variant associated with chemokine receptor gene CCR6, involved in T lymphocyte chemotaxis and expressed by IL17 producing cells. Lymphocytes will be characterised and sorted by polychromatic flow cytometry based upon expression of coreceptors defining T lymphocyte sub-populations, including unconventional populations that we suggest play a key immunoregulatory role, and simultaneously analysed for chemokine receptor expression. Functional studies will examine CCR6 driven chemotaxis and IL17 differentiation in sorted mucosal and systemic T lymphocytes. cDNA from sorted lymphocyte subpopulations will be analysed for chemokine receptor and cytokine expression by qPCR and allele specific expression. Key goals include the definition of chemokine receptor and cytokine expression by populations of unconventional mucosal lymphocytes, and assessing the phenotypic and functional impact of the two Crohn's-associated SNPs on mucosal lymphocytes including the homing and cytokine production of unconventional subpopulations.

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Grant Details

Amount Awarded 268900
Applicant Surname Raine
Approval Committee Clinical Interview Committee
Award Date 2010-07-15T00:00:00+00:00
Financial Year 2009/10
Grant Programme: Title Postdoctoral Training Fellowship for Clinicians
Internal ID 091993/Z/10/Z
Lead Applicant Dr Timothy Raine
Partnership Value 268900
Planned Dates: End Date 2017-07-31T00:00:00+00:00
Planned Dates: Start Date 2011-08-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Dr Miles Parkes, Prof Adrian Hayday, Prof Edwin Chilvers, Prof Rebecca Fitzgerald, Prof Timothy Cox