Journal Article

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

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

2016

Overview

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. TNFSF14 (LIGHT) contributes to airway inflammation and remodelling. Here the authors show that TNFSF14 acting on its receptor TNFRSF14 on mast cells enhances their IgE-dependent activation and that interference with this pathway attenuates features of asthma pathology in mice.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/21 / 13/31 / 13/51 / 14/1 / 59 / 631/250/256/2515 / 631/250/347 / 64 / 64/60 / Airway Remodeling / Animals / Antibodies / Antigens, Dermatophagoides - immunology / Antigens, Dermatophagoides - toxicity / Asthma - chemically induced / Asthma - metabolism / Asthma - pathology / Bronchoalveolar Lavage Fluid - cytology / Female / Gene Expression Regulation - drug effects / Genotype / Humanities and Social Sciences / Immunoglobulin E / Immunoglobulin G / Immunology / Immunotherapy / Life Sciences / Mast Cells - physiology / Mice / Mice, Knockout / multidisciplinary / Ovalbumin - immunology / Ovalbumin - toxicity / Receptors, IgE - genetics / Receptors, IgE - metabolism / Receptors, Tumor Necrosis Factor, Member 14 - genetics / Receptors, Tumor Necrosis Factor, Member 14 - metabolism / Science / Science (multidisciplinary)