title: E-cadherin expression in macrophages dampens their inflammatory responsiveness in vitro, but does not modulate M2-regulated pathologies in vivo.
abstract: IL-4/IL-13-induced alternatively activated macrophages (M(IL-4/IL-13), AAMs or M2) are known to express E-cadherin, enabling them to engage in heterotypic cellular interactions and IL-4-driven macrophage fusion in vitro. Here we show that E-cadherin overexpression in Raw 264.7 macrophages inhibits their inflammatory response to LPS stimulation, as demonstrated by a reduced secretion of inflammatory mediators like interleukin (IL)-6, tumor necrosis factor (TNF) and nitric oxide (NO). To study the function of E-cadherin in M(IL-4/IL-13) macrophages in vivo, we generated macrophage-specific E-cadherin-deficient C57BL/6 mice. Using this new tool, we analyzed immunological parameters during two typical AAM-associated Th2-driven diseases and assessed Th2-associated granuloma formation. Although E-cadherin is strongly induced in AAMs during Taenia crassiceps helminth infections and allergic airway inflammation, its deletion in macrophages does not affect the course of both Th2 cytokine-driven diseases. Moreover, macrophage E-cadherin expression is largely redundant for granuloma formation around Schistosoma mansoni ova. Overall, we conclude that E-cadherin is a valuable AAM marker which suppresses the inflammatory response when overexpressed. Yet E-cadherin deletion in macrophages does not affect M(LPS+IFNγ) and M(IL-4) polarization in vitro, nor in vivo macrophage function, at least in the conditions tested.
authors.affiliation: 1] Laboratory of Myeloid Cell Immunology, VIB, Brussels, Belgium [2] Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van den Bossche
authors.affiliation: 1] Laboratory of Myeloid Cell Immunology, VIB, Brussels, Belgium [2] Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Damya
authors.initials: D
authors.lastname: Laoui
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Naessens
authors.affiliation: Department of Parasitology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Hermelijn H
authors.initials: HH
authors.lastname: Smits
authors.affiliation: Department of Parasitology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Hokke
authors.affiliation: 1] Laboratory of Myeloid Cell Immunology, VIB, Brussels, Belgium [2] Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Benoît
authors.initials: B
authors.lastname: Stijlemans
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Grooten
authors.affiliation: 1] Laboratory of Myeloid Cell Immunology, VIB, Brussels, Belgium [2] Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
authors.affiliation: 1] Laboratory of Myeloid Cell Immunology, VIB, Brussels, Belgium [2] Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Jo A
authors.initials: JA
authors.lastname: Van Ginderachter
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D018893:Bronchoalveolar Lavage; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D003551:Cysticercosis / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012555:Schistosomiasis mansoni / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D015820:Cadherins; D018836:Inflammation Mediators; D018793:Interleukin-13; D015847:Interleukin-4