GPR15-Mediated Homing Controls Immune Homeostasis in the Large Intestine Mucosa

GPR15 Gets Tregs to Guard the Gut The large intestine is the site that is typically most inflamed in Crohn's disease and ulcerative colitis, which are thought to result when the immune system is not able to keep the peace with trillions of resident gut microbes. The immune system does this by recruiting specific cell populations, like regulatory T cells (Tregs), to the gut. Kim et al. (p. 1456, published online 9 May) now suggest that the orphan G protein–coupled receptor GPR15 is expressed by Tregs and required for Treg homing to the large intestine in mice. A G protein–coupled receptor helps to localize regulatory T cells in the large intestine. 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.

• Publication year

  2013

• Venue

  Science

• Publication date

  2013-06-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1126/science.1237013PMID 23661644PMCID PMC3762262
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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