Work

A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice

Year: 2016

Type: article

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 T H 2 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 IgG 1 and 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.

Source: Nature Communications

DOI: 10.1038/ncomms13696

Authors: Riccardo Sibilano, Nicolas Gaudenzio, Marianne K. DeGorter, Laurent L. Reber, Joseph D. Hernandez, Philipp M. Starkl, Oliwia W. Zurek, Mindy Tsai, Sonja Zahner, Stephen B. Montgomery, Axel Roers, Mitchell Kronenberg, Mang Yu, Stephen J. Galli

Institutions: Stanford Medicine, Stanford University, Inserm, Institut Pasteur, Austrian Academy of Sciences, CeMM Research Center for Molecular Medicine, Medical University of Vienna, La Jolla Institute for Immunology, Technische Universität Dresden

Language: English

Topic: Asthma and respiratory diseases

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990

Funders: Philippe Foundation, Austrian Science Fund, National Institutes of Health, Sean N. Parker Center for Allergy and Asthma Research, Stanford University, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences

Awards: G1111767454, G1121861823, G1516365345, Stanford Center for Clinical and Translational Education and Research (SCCTER)UL1, G4484938617, Molecular and Cellular Immunobiology, Mast cells and the immune response against venoms, Neutrophils as therapeutic targets in cryopyrin-associated periodic syndrome, G755810389, G9000005647, G9000058485, G9000095744, Integrated Genomic and Functional Studies of Immunotherapy for Multi-Food Allergy

OpenAlex ID: W2562003319

FWCI: 2.507

Cites: 57

Cited by: 42

Related to: 10