TY - JOUR
T1 - Increased Th2 cytokine secretion, eosinophilic airway inflammation, and airway hyperresponsiveness in neurturin-deficient mice
AU - Michel, Tatiana
AU - Thérésine, Maud
AU - Poli, Aurélie
AU - Domingues, Olivia
AU - Ammerlaan, Wim
AU - Brons, Nicolaas H.C.
AU - Hentges, François
AU - Zimmer, Jacques
PY - 2011/6/1
Y1 - 2011/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79958040758&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1001673
DO - 10.4049/jimmunol.1001673
M3 - Article
AN - SCOPUS:79958040758
SN - 0022-1767
VL - 186
SP - 6497
EP - 6504
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -