Abstract
Emerging evidence suggests that the β2 integrin family of adhesion molecules have an important role in suppressing immune activation and inflammation. β2 integrins are important adhesion and signaling molecules that are exclusively expressed on leukocytes. The four β2 integrins (CD11a, CD11b, CD11c, and CD11d paired with the β2 chain CD18) play important roles in regulating three key aspects of immune cell function: recruitment to sites of inflammation; cell–cell contact formation; and downstream effects on cellular signaling. Through these three processes, β2 integrins both contribute to and regulate immune responses. This review explores the pro- and anti-inflammatory effects of β2 integrins in monocytes, macrophages, and dendritic cells and how they influence the outcome of immune responses. We furthermore discuss how imbalances in β2 integrin function can have far-reaching effects on mounting appropriate immune responses, potentially influencing the development and progression of autoimmune and inflammatory diseases. Therapeutic targeting of β2 integrins, therefore, holds enormous potential in exploring treatment options for a variety of inflammatory conditions.
Highlights
The integrin family of proteins is comprised of 24 heterodimeric transmembrane adhesion receptors
This review explored the opposing nature of β2 integrin pro- and anti-inflammatory functions in three main immune functions, making them prime candidates to be both important mediators and regulators of the immune system
The first is migration, which allows for targeted immune cell recruitment to sites of infection and tissue damage
Summary
The integrin family of proteins is comprised of 24 heterodimeric transmembrane adhesion receptors. Each integrin is formed through the non-covalent association of 1 α-subunit and 1 β-subunit; currently, 16 α-subunits and 8 β-subunits have been identified Their expression on virtually all human cells and their complex signaling mechanisms explain their wide variety of biological roles, including blood clotting, cell adhesion, and migration. Outside-in signaling is initiated by ligand binding to high-affinity integrin receptors (Figure 1). This review will provide an overview of β2 integrin expression on monocytes, macrophages and DCs, before exploring the paradoxical pro-inflammatory and regulatory roles of β2 integrins in immune regulation in three key aspects of immune function: recruitment and migration, cellular interactions, and downstream cell signaling (Figure 3).
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