Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
J Allergy Clin Immunol. 2010 Dec;126(6):1267-76. doi: 10.1016/j.jaci.2010.08.048. Epub 2010 Nov 3.
β7 Integrin, a cell adhesion molecule, is present in the form of α4β7 integrin or αEβ7 integrin. α4β7 Integrin is expressed on most leucocytes and is essential for their migration to gut-associated lymphoid tissues by interacting with its primary ligand, mucosal addressin cell adhesion molecule-1, which is preferentially expressed in gut-associated lymphoid tissues. Although the importance of α4β7 integrin in intestinal inflammation has been established, its role in cutaneous inflammation remains to be elucidated.
We sought to investigate the role of β7 integrin in cutaneous inflammation.
We used a murine contact hypersensitivity model and examined the role of β7 integrin by using β7 integrin-deficient and αE integrin-deficient mice.
β7 Integrin-deficient mice, not αE integrin-deficient mice, are defective in contact hypersensitivity responses. β7 Integrin deficiency does not affect irritant contact dermatitis. The distribution, migration, and function of antigen presenting cells from β7 integrin-deficient mice are comparable to those from wild-type mice. Moreover, sensitized β7 integrin-deficient T cells are able to respond to antigen stimuli in vitro and elicit contact hypersensitivity responses when directly injected into the skin. However, they are defective in reaching the skin under inflammatory conditions, resulting in reduced contact hypersensitivity responses when intravenously injected. Furthermore, intraperitoneal injection of anti-α4β7 integrin neutralizing antibody elicit impaired contact hypersensitivity responses.
α4β7 Integrin contributes to contact hypersensitivity responses by regulating T-cell migration to inflammatory skin.
β7 整合素是一种细胞黏附分子，以α4β7 整合素或αEβ7 整合素的形式存在。α4β7 整合素存在于大多数白细胞上，对于其通过与主要配体黏膜地址素细胞黏附分子-1（优先表达于肠道相关淋巴组织）相互作用迁移到肠道相关淋巴组织是必需的。虽然已经证实α4β7 整合素在肠道炎症中的重要性，但它在皮肤炎症中的作用仍有待阐明。
我们旨在研究β7 整合素在皮肤炎症中的作用。
我们使用了一种小鼠接触性超敏反应模型，并通过使用β7 整合素缺陷型和αE 整合素缺陷型小鼠来研究β7 整合素的作用。
β7 整合素缺陷型小鼠而非αE 整合素缺陷型小鼠在接触性超敏反应反应中存在缺陷。β7 整合素缺陷不影响刺激性接触性皮炎。β7 整合素缺陷型小鼠的抗原呈递细胞的分布、迁移和功能与野生型小鼠相当。此外，致敏的β7 整合素缺陷型 T 细胞能够在体外对抗原刺激作出反应，并在直接注入皮肤时引发接触性超敏反应。然而，它们在炎症条件下不能到达皮肤，导致静脉内注射时接触性超敏反应减少。此外，腹腔内注射抗α4β7 整合素中和抗体可引起接触性超敏反应受损。
α4β7 整合素通过调节 T 细胞向炎症皮肤的迁移来促进接触性超敏反应。
