Cell Signalling Section, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
Semin Immunopathol. 2010 Jun;32(2):173-82. doi: 10.1007/s00281-010-0202-3. Epub 2010 Mar 10.
Integrin binding to ligand plays essential roles in the differentiation and function of mammalian cells. beta2 integrins in leukocytes are needed for migration to sites of inflammation and in lymph nodes as well as for cellular events such as phagocytosis and the formation of the conjugates between T cells and antigen-presenting cells. In T cells, integrin adhesion is activated primarily by the antigen-receptor (TCR complex) and chemokines in a process known as 'inside-out' signalling. Great progress has been made in identifying mutations that are responsible for leukocyte adhesion deficiency (LAD) syndromes, a disorder that presents with an impaired ability to clear pathogens and recurrent life-threatening infections. LAD mutations have been identified with defects in integrins, fucosylation and in the new intracellular mediator kindlin-3. Here, we review the key players in the 'inside-out' and 'outside-in' signalling pathways that will serve as new potential targets in the design of novel therapeutics to treat various immunodeficiencies.
整合素与配体的结合在哺乳动物细胞的分化和功能中起着至关重要的作用。白细胞中的β2 整合素对于迁移到炎症部位和淋巴结以及细胞事件（如吞噬作用和 T 细胞与抗原呈递细胞之间的共轭形成）是必需的。在 T 细胞中，整合素黏附主要通过抗原受体（TCR 复合物）和趋化因子激活，这一过程称为“内向外”信号转导。在识别导致白细胞黏附缺陷（LAD）综合征的突变方面已经取得了很大进展，这种疾病表现为清除病原体和反复发生危及生命的感染的能力受损。已经发现 LAD 突变与整合素、岩藻糖基化以及新的细胞内介质连接蛋白-3 的缺陷有关。在这里，我们回顾了“内向外”和“外向内”信号通路中的关键参与者，它们将成为设计新型治疗剂治疗各种免疫缺陷的新的潜在靶点。
