Cr4

CR4, or complement receptor 4, is an integrin receptor expressed on several types of leukocytes. It is also known as the αXβ2 integrin and is composed of the αX (CD11c) and β2 (CD18) subunits. In humans, the genes ITGAX and ITGB2 encode these subunits, which together form the heterodimer responsible for CR4’s adhesive and phagocytic functions.

CR4 recognizes and binds iC3b, a fragmentation product of complement component C3 that decorates opsonized microbes and particles. Through this interaction, CR4 promotes the phagocytosis of opsonized targets. The receptor can also engage other ligands, including extracellular matrix components, supporting adhesion and cellular migration in tissues.

Functionally, CR4 participates in several innate and adaptive immune processes. It facilitates the recruitment and adhesion of myeloid cells to sites of inflammation, supports uptake and processing of antigens by dendritic cells and macrophages, and contributes to antigen presentation to T cells. CR4 signaling can influence cytoskeletal rearrangements and downstream responses through inside-out and outside-in pathways, modulating cell spreading, migration, and macrophage activation.

Expression and regulation of CR4 are context-dependent. It is prominent on monocytes, macrophages, neutrophils, and dendritic cells, with expression levels influenced by cytokines, chemokines, and cellular activation. Like other integrins, CR4 activity is regulated by divalent cations such as Mg2+ and Ca2+, and by conformational changes that alter affinity for ligands.

Clinical and research relevance centers on CR4’s role in immune defense and inflammatory processes. Altered CR4 activity or expression has been noted in various inflammatory conditions, making it a focus of study for therapies aimed at modulating leukocyte adhesion, migration, or antigen uptake.