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

  1. Jan Van den Bossche1,2,
  2. Bernard Malissen35,
  3. Alberto Mantovani6,7,
  4. Patrick De Baetselier1,2, and
  5. Jo A. Van Ginderachter1,2
  1. 1Myeloid Cell Immunology Laboratory, Vrije Universiteit Brussel, Brussels, Belgium;
  2. 2Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium;
  3. 3Centre d'Immunology de Marseille-Luminy, Université de la Mediterranée, Marseille, France;
  4. 4Inserm U631, Marseille, France;
  5. 5Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6102, Marseille, France;
  6. 6Istituto Clinico Humanitas Istituto di Ricovero e Cura a Carattere Scientifico, Rozzano, Italy; and
  7. 7Department of Translational Medicine, Università degli studi di Milano, Rozzano, Italy

Abstract

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.

  • Submitted October 5, 2011.
  • Accepted December 6, 2011.
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