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