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

Jan Van Den Bossche, Pieter Bogaert, Jolanda Van Hengel, Christopher J. Guérin, Geert Berx, Kiavash Movahedi, Rafael Van Den Bergh, Anna Pereira-Fernandes, Jan M.C. Geuns, Hanspeter Pircher, Pierre Dorny, Johan Grooten, Patrick De Baetselier, Jo A. Van Ginderachter

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)4664-4674
Number of pages11
JournalBlood
Volume114
Issue number21
DOIs
Publication statusPublished - 19 Nov 2009

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