Differential expression of GPR15 on T cells during ulcerative colitis
Alexandra Adamczyk, Daniel Gageik, Annika Frede, Eva Pastille, Wiebke Hansen, Andreas Rueffer, Jan Buer, Jürgen Büning, Jost Langhorst, Astrid M. Westendorf
Alexandra Adamczyk, Daniel Gageik, Annika Frede, Eva Pastille, Wiebke Hansen, Andreas Rueffer, Jan Buer, Jürgen Büning, Jost Langhorst, Astrid M. Westendorf
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Research Article Gastroenterology Immunology

Differential expression of GPR15 on T cells during ulcerative colitis

Abstract

G protein–coupled receptor 15 (GPR15) was recently highlighted as a colon-homing receptor for murine and human CD4+ T cells. The aim of this study was to explore the functional phenotype of human GPR15+CD4+ T cells, focusing on Tregs and effector T cells (Teffs), and to determine whether GPR15 is the driver for the migration of T cells to the colon during ulcerative colitis (UC). In the peripheral blood, GPR15 was expressed on Tregs and Teffs; both GPR15+ T cell subsets produced less IFN-γ and IL-4 but more IL-17 after stimulation and showed a higher migration activity compared with GPR15–CD4+ T cells. In UC patients, GPR15 expression was increased on Tregs in the peripheral blood but not on Teffs. Interestingly, the expression of GPR15 was significantly enhanced on colonic T cells of UC patients in noninflamed biopsies but not in inflamed biopsies. The differential expression of GPR15 in UC patients was accompanied by a significant reduction of bacterial immunoregulatory metabolites in the feces. In conclusion, GPR15 expression on CD4+ T cells is altered in UC patients, which may have implications for the development of therapeutic approaches to target T cell trafficking to the colon.

Authors

Alexandra Adamczyk, Daniel Gageik, Annika Frede, Eva Pastille, Wiebke Hansen, Andreas Rueffer, Jan Buer, Jürgen Büning, Jost Langhorst, Astrid M. Westendorf

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Figure 4

GPR15 expression is diminished in the inflamed tissue of UC patients.

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GPR15 expression is diminished in the inflamed tissue of UC patients. (A...
(A and B) Colonic biopsies of UC patients were isolated from macroscopically inflamed and noninflamed tissue. Expression of (A) GPR15 and (B) FoxP3 in the colonic tissue was determined by quantitative real-time PCR. n = 13. Statistical analysis was performed by Student’s t test (*P < 0.05). (C and D) Colonic biopsies were taken from heathy individuals and from macroscopically inflamed and noninflamed tissue of UC patients. Lymphocytes were isolated from the colonic tissue and stained for expression of (C) FoxP3 on CD4+ T cells and (D) GPR15 expression on CD4+ FoxP3– (Teffs)or CD4+FoxP3+ (Treg) T cells. Representative plots are shown for each cell population, with mean expression ± SD; n = 8–14. GPR15 expression is demonstrated as median (horizontal lines), 25th to 75th percentile (extension of boxes), and range (error bars). Statistical analysis was performed by 1-way ANOVA followed by Tukey’s post-hoc multiple comparison test(*P < 0.05; **P < 0.01; ***P < 0.001).