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

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.

journal_name

Blood

journal_title

Blood

authors

Van den Bossche J,Bogaert P,van Hengel J,Guérin CJ,Berx G,Movahedi K,Van den Bergh R,Pereira-Fernandes A,Geuns JM,Pircher H,Dorny P,Grooten J,De Baetselier P,Van Ginderachter JA

doi

10.1182/blood-2009-05-221598

subject

Has Abstract

pub_date

2009-11-19 00:00:00

pages

4664-74

issue

21

eissn

0006-4971

issn

1528-0020

pii

blood-2009-05-221598

journal_volume

114

pub_type

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