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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Colitis / immunology
  • Colitis / physiopathology*
  • Colon / immunology
  • Colon / physiopathology*
  • Disease Models, Animal
  • Enhancer Elements, Genetic / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation*
  • Gene Knockout Techniques
  • Humans
  • Mice
  • Protein Binding
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Lymphocyte Homing / metabolism*
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism*
  • Species Specificity


  • Forkhead Transcription Factors
  • GPR15 protein, human
  • Gpr15 protein, mouse
  • Receptors, G-Protein-Coupled
  • Receptors, Lymphocyte Homing
  • Receptors, Peptide