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 PMID:23661644  

GPR15-mediated homing controls immune homeostasis in the large intestine mucosa.

Sangwon V Kim | Wenkai V Xiang | Changsoo Kwak | Yi Yang | Xiyao W Lin | Mitsuhiko Ota | Umut Sarpel | Daniel B Rifkin | Ruliang Xu | Dan R Littman
Science (New York, N.Y.) | 2013

Lymphocyte homing, which contributes to inflammation, has been studied extensively in the small intestine, but there is little known about homing to the large intestine, the site most commonly affected in inflammatory bowel disease. GPR15, an orphan heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor, controlled the specific homing of T cells, particularly FOXP3(+) regulatory T cells (Tregs), to the large intestine lamina propria (LILP). GPR15 expression was modulated by gut microbiota and transforming growth factor-β1, but not by retinoic acid. GPR15-deficient mice were prone to develop more severe large intestine inflammation, which was rescued by the transfer of GPR15-sufficient Tregs. Our findings thus describe a T cell-homing receptor for LILP and indicate that GPR15 plays a role in mucosal immune tolerance largely by regulating the influx of Tregs.

Pubmed ID: 23661644

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Associated grants

  • Agency: NCRR NIH HHS, United States
    Id: UL1 RR029893
  • Agency: NCI NIH HHS, United States
    Id: 5P30CA016087-33
  • Agency: NCRR NIH HHS, United States
    Id: UL1RR029893
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI100853
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NCI NIH HHS, United States
    Id: P30 CA016087
  • Agency: NCI NIH HHS, United States
    Id: 5P30CA016087-32
  • Agency: NIAID NIH HHS, United States
    Id: 1T32AI100853-01.
  • Agency: NCI NIH HHS, United States
    Id: P30 CA016087-30

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