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 1

GPR15 is mainly expressed on CD4+ T cells in healthy PBMCs.

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GPR15 is mainly expressed on CD4+ T cells in healthy PBMCs. (A and D) PB...
(A and D) PBMCs from healthy donors were isolated and stained for GPR15 expression on different cell populations: (A) CD4+ T cells, CD8+ T cells, B cells (CD19+ cells); macrophages (Mph; CD14+CD11b+), conventional dendritic cells (cDCs; CD11c+CD123–), and plasmacytoid DCs (pDCs; CD11c–CD123+BDCA-2+) and (D) Teffs (FoxP3–) and Tregs (FoxP3+). Representative plots are shown for each cell population, with mean expression ± SD; n = 12–15. GPR15 expression is summarized as median (horizontal lines), 25th to 75th percentile (extension of boxes), and range (error bars). (B and C) GPR15+ and GPR15–CD4+ T cells were sorted from PBMCs of healthy blood donors and labeled with cell proliferation dye eFluor 670 and stimulated for 3 days. (B) Proliferation of GPR15+ and GPR15–CD4+ T cells was measured by the loss of the eFluor dye. (E) CD25hiCD127loGPR15+ and GPR15–CD4+ Tregs and CD25–CD127hiGPR15+ and GPR15–CD4+ effector T cells (Teffs) were sorted from PBMCs of healthy blood donors and stimulated for 3 days. (C and E) Content of secreted cytokines (IFN-γ, IL-4, and IL-17) in the supernatant was determined by Luminex technology. The amount of secreted cytokines was normalized to 104 cells. Data represent mean ± SEM; 7–12 samples. Statistical analysis was performed by Student’s t test (*P < 0.05; **P < 0.01).