title: The tumor necrosis factor family member LIGHT is a target for asthmatic airway remodeling.
abstract: Individuals with chronic asthma show a progressive decline in lung function that is thought to be due to structural remodeling of the airways characterized by subepithelial fibrosis and smooth muscle hyperplasia. Here we show that the tumor necrosis factor (TNF) family member LIGHT is expressed on lung inflammatory cells after allergen exposure. Pharmacological inhibition of LIGHT using a fusion protein between the IgG Fc domain and lymphotoxin β receptor (LTβR) reduces lung fibrosis, smooth muscle hyperplasia and airway hyperresponsiveness in mouse models of chronic asthma, despite having little effect on airway eosinophilia. LIGHT-deficient mice also show a similar impairment in fibrosis and smooth muscle accumulation. Blockade of LIGHT suppresses expression of lung transforming growth factor-β (TGF-β) and interleukin-13 (IL-13), cytokines implicated in remodeling in humans, whereas exogenous administration of LIGHT to the airways induces fibrosis and smooth muscle hyperplasia, Thus, LIGHT may be targeted to prevent asthma-related airway remodeling.
authors.affiliation: Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Doherty
authors.forename: Pejman
authors.initials: P
authors.lastname: Soroosh
authors.forename: Naseem
authors.initials: N
authors.lastname: Khorram
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Peter
authors.initials: P
authors.lastname: Rosenthal
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cho
authors.forename: Paula S
authors.initials: PS
authors.lastname: Norris
authors.forename: Heonsik
authors.initials: H
authors.lastname: Choi
authors.forename: Stefanie
authors.initials: S
authors.lastname: Scheu
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Zuraw
authors.forename: Carl F
authors.initials: CF
authors.lastname: Ware
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
mesh_terms: D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D018793:Interleukin-13 / Q000502:physiology; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D018793:Interleukin-13; D053361:Lymphotoxin alpha1, beta2 Heterotrimer; C505915:Tnfsf14 protein, mouse; D016212:Transforming Growth Factor beta; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14