Molecular and Integrative Biosciences Research Program, Faculty of Bio- and Environmental Sciences, University of Helsinki, Helsinki, Finland.
Iho- ja Allergiasairaala, HUS, Helsinki, Finland.
Front Immunol. 2019 Feb 19;10:254. doi: 10.3389/fimmu.2019.00254. eCollection 2019.
Beta2-integrins are complex leukocyte-specific adhesion molecules that are essential for leukocyte (e.g., neutrophil, lymphocyte) trafficking, as well as for other immunological processes such as neutrophil phagocytosis and ROS production, and T cell activation. Intriguingly, however, they have also been found to negatively regulate cytokine responses, maturation, and migratory responses in myeloid cells such as macrophages and dendritic cells, revealing new, and unexpected roles of these molecules in immunity. Because of their essential role in leukocyte function, a lack of expression or function of beta2-integrins causes rare immunodeficiency syndromes, Leukocyte adhesion deficiency type I, and type III (LAD-I and LAD-III). LAD-I is caused by reduced or lost expression of beta2-integrins, whilst in LAD-III, beta2-integrins are expressed but dysfunctional because a major integrin cytoplasmic regulator, kindlin-3, is mutated. Interestingly, some LAD-related phenotypes such as periodontitis have recently been shown to be due to an uncontrolled inflammatory response rather than to an uncontrolled infection, as was previously thought. This review will focus on the recent advances concerning the regulation and functions of beta2-integrins in leukocyte trafficking, immune suppression, and immune deficiency disease.
β2 整合素是复杂的白细胞特异性黏附分子，对于白细胞（如中性粒细胞、淋巴细胞）的迁移以及其他免疫过程，如中性粒细胞吞噬和 ROS 产生、T 细胞激活，都是必不可少的。然而，有趣的是，它们也被发现负调节细胞因子反应、髓样细胞（如巨噬细胞和树突状细胞）的成熟和迁移反应，揭示了这些分子在免疫中的新的、意想不到的作用。由于它们在白细胞功能中的重要作用，β2 整合素的缺乏表达或功能会导致罕见的免疫缺陷综合征，包括白细胞黏附缺陷 I 型和 III 型（LAD-I 和 LAD-III）。LAD-I 是由于β2 整合素的表达减少或丧失引起的，而在 LAD-III 中，β2 整合素虽然表达但功能异常，因为一种主要的整合素细胞质调节剂——kindlin-3 发生了突变。有趣的是，最近一些与 LAD 相关的表型，如牙周炎，已经被证明是由于不受控制的炎症反应，而不是以前认为的不受控制的感染。这篇综述将重点介绍β2 整合素在白细胞迁移、免疫抑制和免疫缺陷疾病中的调节和功能的最新进展。
