Regulation and function of the E-cadherin/catenin complex in cells of the monocyte-macrophage lineage and DCs

• Published in: Blood Vol. 119; no. 7; pp. 1623 - 1633
• Main Authors: Van den Bossche, Jan, Malissen, Bernard, Mantovani, Alberto, De Baetselier, Patrick, Van Ginderachter, Jo A.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 16.02.2012; Americain Society of Hematology
• Subjects: Animals; beta Catenin - genetics; beta Catenin - metabolism; beta Catenin - physiology; Biological and medical sciences; Cadherins - genetics; Cadherins - metabolism; Cadherins - physiology; Cell Differentiation - genetics; Cell Differentiation - physiology; Cell Lineage - genetics; Dendritic Cells - metabolism; Dendritic Cells - physiology; Hematologic and hematopoietic diseases; Humans; Immune System - immunology; Immune System - metabolism; Immune System - physiology; Macrophages - metabolism; Macrophages - physiology; Medical sciences; Models, Biological; Monocytes - metabolism; Monocytes - physiology; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Multiprotein Complexes - physiology; Signal Transduction - genetics; Signal Transduction - immunology; Hematology; Monocyte; Cell adhesion molecule; Cell lineage; E Cadherin; Catenin; Macrophage
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2011-10-384289

E-cadherin is best characterized as adherens junction protein, which through homotypic interactions contributes to the maintenance of the epithelial barrier function. In epithelial cells, the cytoplasmic tail of E-cadherin forms a dynamic complex with catenins and regulates several intracellular signal transduction pathways, including Wnt/β-catenin, PI3K/Akt, Rho GTPase, and NF-κB signaling. Recent progress uncovered a novel and critical role for this adhesion molecule in mononuclear phagocyte functions. E-cadherin regulates the maturation and migration of Langerhans cells, and its ligation prevents the induction of a tolerogenic state in bone marrow-derived dendritic cells (DCs). In this respect, the functionality of β-catenin could be instrumental in determining the balance between immunogenicity and tolerogenicity of DCs in vitro and in vivo. Fusion of alternatively activated macrophages and osteoclasts is also E-cadherin–dependent. In addition, the E-cadherin ligands CD103 and KLRG1 are expressed on DC-, T-, and NK-cell subsets and contribute to their interaction with E-cadherin–expressing DCs and macrophages. Here we discuss the regulation, function, and implications of E-cadherin expression in these central orchestrators of the immune system.