Role of beta7 integrins in intestinal lymphocyte homing and retention.
Role of beta7 integrins in intestinal lymphocyte homing and retention.
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DOI：
10.2174/156652409789105525
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发表时间：
2009-09
影响因子：
2.5
通讯作者：
Ley K
中科院分区：
文献类型：
--
作者：
Gorfu G;Rivera-Nieves J;Ley K
参与肠道免疫应答的淋巴细胞存在于肠道相关淋巴组织（GALT）的有组织免疫诱导部位，如派伊尔集合淋巴结（PP）、肠系膜淋巴结（MLN）和肠道上皮和固有层（LP）的弥漫性效应部位。β7整联蛋白负责淋巴细胞在这些部位的有效运输和保留。幼稚和效应淋巴细胞使用α4β7整联蛋白通过与粘蛋白寻址蛋白细胞粘附分子-1（MAdCAM-1）的相互作用从血液外渗至GALT、MLN和LP的肠粘膜组织。αEβ7整联蛋白通过与E-钙粘蛋白相互作用促进效应和记忆淋巴细胞在肠上皮层中的保留。粘液树突状细胞（DC）以视黄酸依赖性方式调节活化的效应和调节淋巴细胞上的肠道归巢受体α4β7整合素和趋化因子受体CCR 9的表达。CD 103（αE整联蛋白）识别MLN和小肠LP中的粘膜DC亚群，其具有增强的诱导应答淋巴细胞上的肠道嗜性受体的能力。β7整合素与其配体之间的相互作用也涉及炎症性肠病（IBD）、肠道寄生虫感染和移植物抗宿主病的发病机制和进展。在肠道炎症过程中，β7整合素依赖性和非依赖性途径有助于淋巴细胞募集到肠道组织和疾病发病机制。最近的工作已经探索了IBD中α4和β7整联蛋白的治疗靶向的潜力。在此，我们回顾了目前对β7整合素在健康和疾病中肠道淋巴细胞运输和滞留中的作用的认识。
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). 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.
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