title: A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice.
abstract: Asthma has multiple features, including airway hyperreactivity, inflammation and remodelling. The TNF superfamily member TNFSF14 (LIGHT), via interactions with the receptor TNFRSF14 (HVEM), can support TH2 cell generation and longevity and promote airway remodelling in mouse models of asthma, but the mechanisms by which TNFSF14 functions in this setting are incompletely understood. Here we find that mouse and human mast cells (MCs) express TNFRSF14 and that TNFSF14:TNFRSF14 interactions can enhance IgE-mediated MC signalling and mediator production. In mouse models of asthma, TNFRSF14 blockade with a neutralizing antibody administered after antigen sensitization, or genetic deletion of Tnfrsf14, diminishes plasma levels of antigen-specific IgG1and IgE antibodies, airway hyperreactivity, airway inflammation and airway remodelling. Finally, by analysing two types of genetically MC-deficient mice after engrafting MCs that either do or do not express TNFRSF14, we show that TNFRSF14 expression on MCs significantly contributes to the development of multiple features of asthma pathology.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sibilano
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gaudenzio
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.|Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Marianne K
authors.initials: MK
authors.lastname: DeGorter
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.|Department of Immunology, Unit of Antibodies in Therapy and Pathology, INSERM U1222, Institut Pasteur, Paris 75015, France.
authors.forename: Laurent L
authors.initials: LL
authors.lastname: Reber
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.|Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Hernandez
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and Department of Medicine I, Research Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Starkl
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Oliwia W
authors.initials: OW
authors.lastname: Zurek
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Mindy
authors.initials: M
authors.lastname: Tsai
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Sonja
authors.initials: S
authors.lastname: Zahner
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.|Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Montgomery
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Dresden 01307, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Mang
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.|Department of Microbiology and Immunology and Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D000906:Antibodies; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000633:toxicity; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D007073:Immunoglobulin E; D007074:Immunoglobulin G; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; D039741:Antigens, Dermatophagoides; D007074:Immunoglobulin G; D017455:Receptors, IgE; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506029:Tnfrsf14 protein, mouse; D007073:Immunoglobulin E; D010047:Ovalbumin