Regulation of CD25 expression and IBD risk (360G-Wellcome-211839_Z_18_Z)

The inflammatory bowel diseases (IBD) Crohn’s disease (CD) and ulcerative colitis (UC) are chronic disorders of the gastrointestinal tract affecting 1 in 400 people in the UK. Both have a complex aetiology involving genetic predisposition and environmental triggers which is not yet fully understood, but may result in persistent bacterial infection, defective mucosal barrier, or a dysregulated immune response. Genome-wide association scans (GWAS) have identified over 200 IBD-associated loci (Lui et al 2015). One locus encompasses the gene encoding the IL-2 receptor alpha chain (CD25). CD25 is expressed by activated T cells and important in signalling pathways that regulate the immune response. Our fine-mapping data (Huang et al 2017) show that the GWAS signal at IL2RA/CD25 is due to a single SNP associated with CD, in intron 1 of the gene and co-localising with a super enhancer that regulates expression (Fahr et al 2015). This SNP is also associated with Type 1 diabetes and multiple other autoimmune disorders. In this study we will identify additional recently recruited IBD patients who are homozygous for the CD risk allele at this SNP by genotyping and investigate alteration in the expression of IL2RA by qPCR in flow-sorted regulatory and effector T cells.