TY - JOUR
T1 - Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes
AU - Van Den Bossche, Jan
AU - Bogaert, Pieter
AU - Van Hengel, Jolanda
AU - Guérin, Christopher J.
AU - Berx, Geert
AU - Movahedi, Kiavash
AU - Van Den Bergh, Rafael
AU - Pereira-Fernandes, Anna
AU - Geuns, Jan M.C.
AU - Pircher, Hanspeter
AU - Dorny, Pierre
AU - Grooten, Johan
AU - De Baetselier, Patrick
AU - Van Ginderachter, Jo A.
PY - 2009/11/19
Y1 - 2009/11/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=73949140039&partnerID=8YFLogxK
U2 - 10.1182/blood-2009-05-221598
DO - 10.1182/blood-2009-05-221598
M3 - Article
C2 - 19726720
AN - SCOPUS:73949140039
VL - 114
SP - 4664
EP - 4674
JO - Blood
JF - Blood
SN - 0006-4971
IS - 21
ER -