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

Linh P. Nguyen, Junliang Pan, Thanh Theresa Dinh, Husein Hadeiba, Edward O'hara, Ahmad Ebtikar, Arnulf Hertweck, M. Refik Gökmen, Graham M. Lord, Richard G. Jenner, Eugene C. Butcher, Aida Habtezion

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)207-213
Number of pages7
JournalNature Immunology
Volume16
Issue number2
DOIs
Publication statusPublished - 22 Dec 2014

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