Blood Journal
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Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes

  1. Jan Van den Bossche1,2,
  2. Pieter Bogaert3,
  3. Jolanda van Hengel4,5,
  4. Christopher J. Guérin4,6,
  5. Geert Berx4,7,
  6. Kiavash Movahedi1,2,
  7. Rafael Van den Bergh1,2,
  8. Anna Pereira-Fernandes1,2,
  9. Jan M. C. Geuns8,
  10. Hanspeter Pircher9,
  11. Pierre Dorny10,
  12. Johan Grooten3,
  13. Patrick De Baetselier1,2, and
  14. Jo A. Van Ginderachter1,2
  1. 1Department of Molecular and Cellular Interactions, VIB and
  2. 2Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium;
  3. 3Laboratory of Molecular Immunology, Department of Molecular Biomedical Research and
  4. 4Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium;
  5. 5Molecular Cell Biology Unit,
  6. 6Microscopy Core Facility, and
  7. 7Unit of Molecular and Cellular Oncology, Department for Molecular Biomedical Research, VIB, Ghent, Belgium;
  8. 8Laboratory of Functional Biology, KU Leuven, Heverlee, Belgium;
  9. 9Department of Immunology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany; and
  10. 10Department of Animal Health, Institute of Tropical Medicine, Antwerp, Belgium

Abstract

Alternatively activated macrophages (AAMs), triggered by interleukin-4 (IL-4) and IL-13, play a modulating role during Th2 cytokine-driven pathologies, but their molecular armament remains poorly characterized. Here, we established E-cadherin (Cdh1) as a selective marker for IL-4/IL-13–exposed mouse and human macrophages, which is STAT6-dependently induced during polarized Th2 responses associated with Taenia crassiceps helminth infections or allergic airway inflammation. The IL-4–dependent, arginase-1/ornithine decarboxylase–mediated production of polyamines is important for maximal Cdh1 induction, unveiling a novel mechanism for IL-4–dependent gene transcription. At the macrophage surface, E-cadherin forms a functional complex with the catenins that accumulates at sites of cell contact. Macrophage-specific deletion of the Cdh1 gene illustrates the implication of E-cadherin in IL-4–driven macrophage fusion and heterotypic interactions with CD103+ and KLRG1+ T cells. This study identifies the E-cadherin/catenin complex as a discriminative, partly polyamine-regulated feature of IL-4/IL-13–exposed alternatively activated macrophages that contributes to homotypic and heterotypic cellular interactions.

  • Submitted May 14, 2009.
  • Accepted August 11, 2009.
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