title: Role and species-specific expression of colon T cell homing receptor GPR15 in colitis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Linh P
authors.initials: LP
authors.lastname: Nguyen
authors.affiliation: 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.
authors.forename: Junliang
authors.initials: J
authors.lastname: Pan
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Theresa Thanh
authors.initials: TT
authors.lastname: Dinh
authors.affiliation: 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.
authors.forename: Husein
authors.initials: H
authors.lastname: Hadeiba
authors.affiliation: 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.
authors.forename: Edward
authors.initials: E
authors.lastname: O'Hara
authors.affiliation: 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.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Ebtikar
authors.affiliation: UCL Cancer Institute, University College London, London, W1T 4JF, United Kingdom.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Hertweck
authors.affiliation: 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.
authors.forename: M Refik
authors.initials: MR
authors.lastname: Gökmen
authors.affiliation: 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.
authors.forename: Graham M
authors.initials: GM
authors.lastname: Lord
authors.affiliation: UCL Cancer Institute, University College London, London, W1T 4JF, United Kingdom.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Jenner
authors.affiliation: 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.
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Aida
authors.initials: A
authors.lastname: Habtezion
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology / Q000503:physiopathology*; D003106:Colon / Q000276:immunology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004742:Enhancer Elements, Genetic / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006801:Humans; D051379:Mice; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D051858:Forkhead Transcription Factors; C103539:GPR15 protein, human; C523001:Gpr15 protein, mouse; D043562:Receptors, G-Protein-Coupled; D016201:Receptors, Lymphocyte Homing; D018000:Receptors, Peptide