1. GPR15: a tale of two species
- Author
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Joanne L. Viney and Janine Bilsborough
- Subjects
Regulation of gene expression ,Receptors, Peptide ,Colon ,Effector ,Regulatory T cell ,Immunology ,Receptors, Lymphocyte Homing ,Biology ,Colitis ,Article ,Receptors, G-Protein-Coupled ,Cell biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Mucosal immunology ,medicine ,Animals ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,IL-2 receptor ,Receptor ,Homing (hematopoietic) - 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 their trafficking to the colon. In humans GPR15 is expressed by effector cells including pathogenic TH2 cells in ulcerative colitis, but is not expressed by 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 expression. Our results highlight species differences in GPR15 regulation, and suggest it as a potential therapeutic target for colitis.
- Published
- 2015
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