A single nucleotide polymorphism in the gene for GPR183 increases its surface expression on blood lymphocytes of patients with inflammatory bowel disease

• Published in: British journal of pharmacology Vol. 178; no. 16; pp. 3157 - 3175
• Main Authors: Ruiz, Florian, Wyss, Annika, Rossel, Jean‐Benoît, Sulz, Michael Christian, Brand, Stephan, Moncsek, Anja, Mertens, Joachim C., Roth, René, Clottu, Aurélie S., Burri, Emanuel, Juillerat, Pascal, Biedermann, Luc, Greuter, Thomas, Rogler, Gerhard, Pot, Caroline, Misselwitz, Benjamin
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-08-2021
• Subjects: Alleles; Animal models; CCL20 protein; CCR6 protein; CCR9 protein; Chemokine receptors; Colitis; Crohn's disease; Disease; Epstein-Barr virus; FACS; Flow cytometry; Gene polymorphism; Genetic Predisposition to Disease; Genotype; GPR183/EBI2; Helper cells; Humans; IBD; Immunological memory; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - genetics; Intestine; Leukocyte migration; Leukocytes (mononuclear); Ligands; Lymphocytes; Lymphocytes T; Memory cells; Peripheral blood mononuclear cells; Polymorphism; Polymorphism, Single Nucleotide; Psoriasis; Receptors, G-Protein-Coupled - genetics; Single-nucleotide polymorphism; SNP; UBAC2; Ulcerative colitis; GPR183/EBI2; IBD; FACS; SNP; psoriasis; UBAC2
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.15395

Background and Purpose
Single nucleotide polymorphism rs9557195 within the gene of the G protein‐coupled receptor Epstein‐Barr virus‐induced gene 2 (EBI2/GPR183) has been associated with increased risk for inflammatory bowel diseases (IBD). GPR183 mediates the migration of intestinal immune cells and promotes colitis in animal models. Here, we study GPR183 surface expression of immune cells and associations of rs9557195 with GPR183 expression and IBD disease course.
Experimental Approach
We recruited 27 IBD patients (15 with ulcerative colitis [UC] and 12 with Crohn's disease [CD]) and eight healthy volunteers (HV). GPR183 expression was measured by FACS in subtypes of peripheral blood mononuclear cells. We analysed IBD disease course in 2301 patients (1335 with CD and 966 with UC) of the Swiss IBD cohort study.
Key Results
We found increased GPR183 expression in lymphocytes expressing chemokine receptors CCR6 or CCR9, implicated in IBD and on Th17 memory T cells. The GPR183 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 GPR183 surface expression compared to individuals with the TT allele. Swiss IBD cohort study patients carrying the rs9557195‐CC allele had higher psoriasis rates compared to individuals with the TT allele.
Conclusion and Implications
We demonstrate increased GPR183 surface expression on T cells with a potential role in gut inflammation. An SNP of the GPR183 locus was associated with GPR183 surface expression and psoriasis rates in IBD patients. Our data suggest a pro‐inflammatory role of GPR183 in IBD.
LINKED ARTICLES
This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc