Role of beta7 integrins in intestinal lymphocyte homing and retention.
Lymphocytes involved in intestinal immune response are found in organized immune inductive sites of the gut-associated lymphoid tissues (GALT) such as Peyer's patches (PP), mesenteric lymph nodes (MLN) and diffuse effector sites of gut epithelium and lamina propria (LP). beta(7) integrins are responsible for efficient trafficking and retention of lymphocytes in these sites. Naïve and effector lymphocytes use alpha(4)beta(7) integrin to extravasate from blood to gut mucosal tissues of GALT, MLN and LP via interactions with Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1). The alpha(E)beta(7) integrin facilitates retention of effector and memory lymphocytes in the gut epithelial layer via interactions with E-cadherin. Mucosal dendritic cells (DCs) regulate the expression of the gut homing receptors alpha(4)beta(7) integrin and the chemokine receptor CCR9 on activated effector and regulatory lymphocytes in a retinoic acid-dependent manner. CD103 (alpha(E) integrin) identifies a subset of mucosal DCs in MLN and small intestine LP that have an enhanced ability to induce gut-tropic receptors on responding lymphocytes. The interactions between beta(7) integrin and their ligands are also implicated in the pathogenesis and progression of inflammatory bowel diseases (IBDs), intestinal parasitic infections and graft-versus-host diseases. During intestinal inflammation, beta(7) integrin-dependent and -independent pathways contribute to lymphocytes recruitment to the intestinal tissues and disease pat-hogenesis. Recent works have explored the potential of therapeutic targeting of alpha(4) and beta(7) integrins in IBDs. Here, we review the current understanding of the role of beta(7) integrins in intestinal lymphocyte trafficking and retention in health and disease.
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
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G
Gorfu
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Rivera-Nieves
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K
Ley
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015820:Cadherins / Q000276:immunology; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D039001:Integrin alpha Chains / Q000276:immunology; D039441:Integrin alpha4 / Q000276:immunology; D039641:Integrin beta Chains / Q000276:immunology*; D007422:Intestines / Q000166:cytology* / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000502:physiology; D009088:Mucoproteins / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D015820:Cadherins; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; C504265:MADCAM1 protein, human; D009088:Mucoproteins; C091367:alpha E integrins; C091368:integrin beta7; D039441:Integrin alpha4