Publication Date:
2013-05-11
Description:
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-beta1, 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762262/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762262/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Sangwon V -- Xiang, Wenkai V -- Kwak, Changsoo -- Yang, Yi -- Lin, Xiyao W -- Ota, Mitsuhiko -- Sarpel, Umut -- Rifkin, Daniel B -- Xu, Ruliang -- Littman, Dan R -- 1T32AI100853-01./AI/NIAID NIH HHS/ -- 5P30CA016087-32/CA/NCI NIH HHS/ -- 5P30CA016087-33/CA/NCI NIH HHS/ -- P30 CA016087/CA/NCI NIH HHS/ -- P30 CA016087-30/CA/NCI NIH HHS/ -- T32 AI100853/AI/NIAID NIH HHS/ -- UL1 RR029893/RR/NCRR NIH HHS/ -- UL1RR029893/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jun 21;340(6139):1456-9. doi: 10.1126/science.1237013. Epub 2013 May 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23661644" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Citrobacter rodentium
;
Colitis/immunology
;
Colon/immunology
;
Enterobacteriaceae Infections/immunology
;
Helicobacter Infections/immunology
;
Homeostasis
;
Humans
;
Immune Tolerance
;
Intestinal Mucosa/*immunology
;
Intestine, Large/*immunology/microbiology
;
Intestine, Small/immunology
;
Metagenome/physiology
;
Mice
;
Mice, Knockout
;
Mice, Transgenic
;
Receptors, G-Protein-Coupled/genetics/*metabolism
;
Receptors, Lymphocyte Homing/*metabolism
;
Receptors, Peptide/genetics/*metabolism
;
T-Lymphocytes, Regulatory/*immunology/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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