The single nucleotide polymorphism rs9557195 within the gene Epstein-Barr virus-induced G protein-coupled receptor 2 (EBI2) has been associated with increased risk for inflammatory bowel diseases (IBD). EBI2 mediates migration of intestinal immune cells and promotes colitis in animal models. Here we study EBI2 surface expression of immune cells and associations of rs9557195 with EBI2 expression and IBD disease course.
We recruited 27 IBD patients (15 with ulcerative colitis (UC), 12 with Crohn's disease (CD)), and 8 healthy volunteers (HV). EBI2 expression was measured by fluorescence activated cell sorting in subtypes of peripheral blood mononuclear cells. We further analyzed IBD disease course in 2301 patients (1335 with CD and 966 with UC) of the Swiss IBD cohort study (SIBDCS).
We found increased EBI2 expression in lymphocytes expressing chemokine receptors CCR6 or CCR9, implicated in IBD and on Th17 memory T cells. The EBI2 ligand 7α,25-dihydroxycholesterol and the CCR6 ligand CCL20 stimulated migration of memory T cells in an additive manner. Further, IBD patients with the CC allele of rs9557195 had higher EBI2 surface expression compared to individuals with the TT allele. SIBDC patients carrying the rs9557195-CC allele had higher psoriasis rates compared to individuals with the TT allele.
We demonstrate increased EBI2 surface expression on T cells with a potential role in gut inflammation. A SNP of the EBI2 locus was associated with EBI2 surface expression and psoriasis rates in IBD patients. Our data suggest a pro-inflammatory role of EBI2 in IBD.