Abstract
β2 integrins are heterodimeric surface receptors composed of a variable α (CD11a-CD11d) and a constant β (CD18) subunit and are specifically expressed by leukocytes. The α subunit defines the individual functional properties of the corresponding β2 integrin, but all β2 integrins show functional overlap. They mediate adhesion to other cells and to components of the extracellular matrix (ECM), orchestrate uptake of extracellular material like complement-opsonized pathogens, control cytoskeletal organization, and modulate cell signaling. This review aims to delineate the tremendous role of β2 integrins for immune functions as exemplified by the phenotype of LAD-I (leukocyte adhesion deficiency 1) patients that suffer from strong recurrent infections. These immune defects have been largely attributed to impaired migratory and phagocytic properties of polymorphonuclear granulocytes. The molecular base for this inherited disease is a functional impairment of β2 integrins due to mutations within the CD18 gene. LAD-I patients are also predisposed for autoimmune diseases. In agreement, polymorphisms within the CD11b gene have been associated with autoimmunity. Consequently, β2 integrins have received growing interest as targets in the treatment of autoimmune diseases. Moreover, β2 integrin activity on leukocytes has been implicated in tumor development.
Highlights
Integrins are evolutionarily conserved heterodimeric transmembrane receptors that consist of an α and a β subunit [1]
This review aims to highlight the role of β2 integrins in innate and adaptive immune cells since this group of receptors is crucially involved in leukocyte differentiation, activation/polarization, and functional activity
Concerning the role of β2 integrins expressed by antigen presenting cells (APC) in the context of T cell activation, we reported for conventional dendritic cells (DC) that MAC-1 when activated by divalent cations attenuated CD4+ T cell proliferation [24]
Summary
Integrins are evolutionarily conserved heterodimeric transmembrane receptors that consist of an α and a β subunit [1]. NMuAmCer-o1ubsincedlsl snuurfmaceeroruecsepcetlolrssuartfhacigehraefficenpittoyrsstaattehaingdh affinity state and numerous soluble ligands irrespective of its state of activation The former group comprises ICAM1-4, VCAM-1 (Vascular cell adhesion protein 1), JAM-3 (Junctional adhesion molecule 3), Thy-1 (Thymus cell antigen 1), RAGE (Receptor for advanced glycation endproducts), DC-SIGN (Dendritic cell-specific ICAM-3-grabbing non-integrin), and CD40L [41]. The list of MAC1 binding soluble ligands is quite extensive, and includes fibrin(ogen), Factor Xa, platetelet Ib, numerous soluble ligands irrespective of its state of activation CD11d/CD18 is highly expressed on NK cells, B cells, and γδT cells as well [67]
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