title: Leukocyte Trafficking to the Small Intestine and Colon.
abstract: Leukocyte trafficking to the small and large intestines is tightly controlled to maintain intestinal immune homeostasis, mediate immune responses, and regulate inflammation. A wide array of chemoattractants, chemoattractant receptors, and adhesion molecules expressed by leukocytes, mucosal endothelium, epithelium, and stromal cells controls leukocyte recruitment and microenvironmental localization in intestine and in the gut-associated lymphoid tissues (GALTs). Naive lymphocytes traffic to the gut-draining mesenteric lymph nodes where they undergo antigen-induced activation and priming; these processes determine their memory/effector phenotypes and imprint them with the capacity to migrate via the lymph and blood to the intestines. Mechanisms of T-cell recruitment to GALT and of T cells and plasmablasts to the small intestine are well described. Recent advances include the discovery of an unexpected role for lectin CD22 as a B-cell homing receptor GALT, and identification of the orphan G-protein-coupled receptor 15 (GPR15) as a T-cell chemoattractant/trafficking receptor for the colon. GPR15 decorates distinct subsets of T cells in mice and humans, a difference in species that could affect translation of the results of mouse colitis models to humans. Clinical studies with antibodies to integrin α4β7 and its vascular ligand mucosal vascular addressin cell adhesion molecule 1 are proving the value of lymphocyte trafficking mechanisms as therapeutic targets for inflammatory bowel diseases. In contrast to lymphocytes, cells of the innate immune system express adhesion and chemoattractant receptors that allow them to migrate directly to effector tissue sites during inflammation. We review the mechanisms for innate and adaptive leukocyte localization to the intestinal tract and GALT, and discuss their relevance to human intestinal homeostasis and inflammation.
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California. Electronic address: aidah@stanford.edu.
authors.forename: Aida
authors.initials: A
authors.lastname: Habtezion
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.
authors.forename: Linh P
authors.initials: LP
authors.lastname: Nguyen
authors.affiliation: The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, The Palo Alto Veterans Institute for Research, Palo Alto, California.
authors.forename: Husein
authors.initials: H
authors.lastname: Hadeiba
authors.affiliation: The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, The Palo Alto Veterans Institute for Research, Palo Alto, California; Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California. Electronic address: ebutcher@stanford.edu.
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D002634:Chemotaxis, Leukocyte; D003106:Colon / Q000276:immunology* / Q000378:metabolism; D004751:Enteritis / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
keywords: Adhesion Molecules; Chemokine Receptors; Intestine; Leukocyte Trafficking