May 7, 2014

Generation of primary human intestinal T cell transcriptomes reveals differential expression at genetic risk loci for immune-mediated disease

Gut
Tim RaineArthur Kaser

Abstract

Genome-wide association studies (GWAS) have identified genetic variants within multiple risk loci as predisposing to intestinal inflammatory diseases, including Crohn's disease, ulcerative colitis and coeliac disease. Most risk variants affect regulation of transcription, but a critical challenge is to identify which genes and which cell types these variants affect. We aimed to characterise whole transcriptomes for each common T lymphocyte subset resident within the gut mucosa, and use these to infer biological insights and highlight candidate genes of interest within GWAS risk loci. We isolated the four major intestinal T cell populations from pinch biopsies from healthy subjects and generated transcriptomes for each. We computationally integrated these transcriptomes with GWAS data from immune-related diseases. Robust, high quality transcriptomic data were generated from 1 ng of RNA from precisely sorted cell subsets. Gene expression patterns clearly differentiated intestinal T cells from counterparts in peripheral blood and revealed distinct signalling pathways for each intestinal T cell subset. Intestinal-specific T cell transcripts were enriched in GWAS risk loci for Crohn's disease, ulcerative colitis and coeliac disease,...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Biochemical Pathway
IIeocolitis
T-Lymphocyte
Immune System Diseases
Peripheral Blood
Candidate Disease Gene
Ileum
Bio-Informatics
Immunity, Mucosal

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