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Nat Immunol. 2015 Feb;16(2):207-213. doi: 10.1038/ni.3079. Epub 2014 Dec 22.

Role and species-specific expression of colon T cell homing receptor GPR15 in colitis.

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Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System and The Palo Alto Veterans Institute for Research, Palo Alto, California 94304, USA.
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
UCL Cancer Institute, University College London, London, W1T 4JF, United Kingdom.
Department of Experimental Immunobiology and NIHR Comprehensive Biomedical Research Centre, Guy's and St. Thomas' Hospital and King's College London, London, SE1 9RT, United Kingdom.
Contributed equally


Lymphocyte recruitment maintains intestinal immune homeostasis but also contributes to inflammation. The orphan chemoattractant receptor GPR15 mediates regulatory T cell homing and immunosuppression in the mouse colon. We show that GPR15 is also expressed by mouse TH17 and TH1 effector cells and is required for colitis in a model that depends on the trafficking of these cells to the colon. In humans GPR15 is expressed by effector cells, including pathogenic TH2 cells in ulcerative colitis, but is expressed poorly or not at all by colon regulatory T (Treg) cells. The TH2 transcriptional activator GATA-3 and the Treg-associated transcriptional repressor FOXP3 robustly bind human, but not mouse, GPR15 enhancer sequences, correlating with receptor expression. Our results highlight species differences in GPR15 regulation and suggest it as a potential therapeutic target for colitis.

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