Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes.
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.
Van den Bossche
Jan
J
Department of Molecular and Cellular Interactions, VIB-Vrije Universiteit Brussel, Building E,Level 8, Pleinlaan 2, B-1050, Brussels, Belgium.
Bogaert
Pieter
P
van Hengel
Jolanda
J
Guérin
Christopher J
CJ
Berx
Geert
G
Movahedi
Kiavash
K
Van den Bergh
Rafael
R
Pereira-Fernandes
Anna
A
Geuns
Jan M C
JM
Pircher
Hanspeter
H
Dorny
Pierre
P
Grooten
Johan
J
De Baetselier
Patrick
P
Van Ginderachter
Jo A
JA
D000818:Animals; D001249:Asthma / Q000276:immunology; D015153:Blotting, Western; D015820:Cadherins / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D047468:Immunoprecipitation; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D011073:Polyamines / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013622:Taeniasis / Q000276:immunology; D051178:alpha Catenin / Q000276:immunology* / Q000378:metabolism
D015820:Cadherins; D018793:Interleukin-13; D011073:Polyamines; D051178:alpha Catenin; D015847:Interleukin-4