Role of β7 Integrins in Intestinal Lymphocyte Homing and Retention

G.      Gorfu; J.      Rivera-Nieves; K.      Ley

doi:10.2174/156652409789105525

Abstract

Lymphocytes involved in intestinal immune response are found in organized immune inductive sites of the gut-associated lymphoid tissues (GALT) such as Peyers patches (PP), mesenteric lymph nodes (MLN) and diffuse effector sites of gut epithelium and lamina propria (LP). β7 integrins are responsible for efficient trafficking and retention of lymphocytes in these sites. Naïve and effector lymphocytes use α4β7 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 αEβ7 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 α4β7 integrin and the chemokine receptor CCR9 on activated effector and regulatory lymphocytes in a retinoic acid-dependent manner. CD103 (αE 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 β7 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, β7 integrin-dependent and - independent pathways contribute to lymphocytes recruitment to the intestinal tissues and disease pathogenesis. Recent works have explored the potential of therapeutic targeting of α4 and β7 integrins in IBDs. Here, we review the current understanding of the role of β7 integrins in intestinal lymphocyte trafficking and retention in health and disease.

Keywords: Integrins, homing, retention, lymphocytes, intestinal tissues, intestinal inflammation

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