Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes
2009; Elsevier BV; Volume: 114; Issue: 21 Linguagem: Inglês
10.1182/blood-2009-05-221598
ISSN1528-0020
AutoresJan Van den Bossche, Pieter Bogaert, Jolanda van Hengel, Christopher J. Guérin, Geert Berx, Kiavash Movahedi, Rafaël Van den Bergh, Anna Pereira-Fernandes, Jan M.C. Geuns, Hanspeter Pircher, Pierre Dorny, Johan Grooten, Patrick De Baetselier, Jo A. Van Ginderachter,
Tópico(s)Mast cells and histamine
ResumoAbstract 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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