Generation of primary human intestinal T cell transcriptomes reveals differential expression at genetic risk loci for immune-mediated disease.
Bottom Line: Gene expression patterns clearly differentiated intestinal T cells from counterparts in peripheral blood and revealed distinct signalling pathways for each intestinal T cell subset.We have demonstrated that careful processing of mucosal biopsies allows the generation of transcriptomes from as few as 1000 highly purified cells with minimal interindividual variation.Bioinformatic integration of transcriptomic data with recent GWAS data identified specific candidate genes and cell types for inflammatory pathologies.
Affiliation: Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.Show MeSH
Related in: MedlinePlus
Mentions: We next tested a number of diseases where the inflammatory pathology occurs outside of the intestine. We did not detect any significant enrichment for asthma, primary biliary cirrhosis, rheumatoid arthritis or systemic lupus erythematosus. However, there was a highly significant overlap between Type 1 diabetes (T1D)-associated loci and genes upregulated in CD4+ and CD8+ LPLs and CD8+ IELs. Likewise, we found significant overlap for psoriasis risk loci and genes upregulated in both LPL TEM populations; for multiple sclerosis (MS), risk loci showed significant overlap with genes upregulated in CD4+ LPL TEM cells, but also with genes downregulated in CD8+ IEL and LPL TEM cell populations. Several of these immune diseases share multiple genetic susceptibility loci. However, the enrichment around SNPs associated with extraintestinal pathology was not solely restricted to those genetic loci shared with GI inflammatory diseases (figure 4).
Affiliation: Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.