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Blood, 19 November 2009, Vol. 114, No. 21, pp. 4664-4674. Prepublished online as a Blood First Edition Paper on September 2, 2009; DOI 10.1182/blood-2009-05-221598.
IMMUNOBIOLOGY Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes1 Department of Molecular and Cellular Interactions, VIB and 2 Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; 3 Laboratory of Molecular Immunology, Department of Molecular Biomedical Research and 4 Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; 5 Molecular Cell Biology Unit, 6 Microscopy Core Facility, and 7 Unit of Molecular and Cellular Oncology, Department for Molecular Biomedical Research, VIB, Ghent, Belgium; 8 Laboratory of Functional Biology, KU Leuven, Heverlee, Belgium; 9 Department of Immunology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany; and 10 Department of Animal Health, Institute of Tropical Medicine, Antwerp, Belgium 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.
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