Differential expression of GPR15 on T cells during ulcerative colitis
Alexandra Adamczyk ... Jost Langhorst, Astrid M. Westendorf
Alexandra Adamczyk ... Jost Langhorst, Astrid M. Westendorf
Published April 20, 2017
Citation Information: JCI Insight. 2017;2(8):e90585. doi:10.1172/jci.insight.90585.
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Categories: 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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GPR15 is mainly expressed on CD4+ T cells in healthy PBMCs. (A and D) PB...

Figure 1

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

(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).