title: Increased Th2 cytokine secretion, eosinophilic airway inflammation, and airway hyperresponsiveness in neurturin-deficient mice.
abstract: Neurotrophins such as nerve growth factor and brain-derived neurotrophic factor have been described to be involved in the pathogenesis of asthma. Neurturin (NTN), another neurotrophin from the glial cell line-derived neurotrophic factor family, was shown to be produced by human immune cells: monocytes, B cells, and T cells. Furthermore, it was previously described that the secretion of inflammatory cytokines was dramatically stimulated in NTN knockout (NTN(-/-)) mice. NTN is structurally similar to TGF-β, a protective cytokine in airway inflammation. This study investigates the implication of NTN in a model of allergic airway inflammation using NTN(-/-) mice. The bronchial inflammatory response of OVA-sensitized NTN(-/-) mice was compared with wild-type mice. Airway inflammation, Th2 cytokines, and airway hyperresponsiveness (AHR) were examined. NTN(-/-) mice showed an increase of OVA-specific serum IgE and a pronounced worsening of inflammatory features. Eosinophil number and IL-4 and IL-5 concentration in the bronchoalveolar lavage fluid and lung tissue were increased. In parallel, Th2 cytokine secretion of lung draining lymph node cells was also augmented when stimulated by OVA in vitro. Furthermore, AHR was markedly enhanced in NTN(-/-) mice after sensitization and challenge when compared with wild-type mice. Administration of NTN before challenge with OVA partially rescues the phenotype of NTN(-/-) mice. These findings provide evidence for a dampening role of NTN on allergic inflammation and AHR in a murine model of asthma.
authors.affiliation: Laboratoire d'Immunogénétique et d'Allergologie, Centre de Recherche Public de la Santé, L-1526 Luxembourg, Luxembourg. tatiana.michel@crp-sante.lu
authors.forename: Tatiana
authors.initials: T
authors.lastname: Michel
authors.forename: Maud
authors.initials: M
authors.lastname: Thérésine
authors.forename: Aurélie
authors.initials: A
authors.lastname: Poli
authors.forename: Olivia
authors.initials: O
authors.lastname: Domingues
authors.forename: Wim
authors.initials: W
authors.lastname: Ammerlaan
authors.forename: Nicolaas H C
authors.initials: NH
authors.lastname: Brons
authors.forename: François
authors.initials: F
authors.lastname: Hentges
authors.forename: Jacques
authors.initials: J
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051101:Neurturin / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; D016207:Cytokines; C494991:Gfra2 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051101:Neurturin; C495056:Nrtn protein, mouse; D010047:Ovalbumin