Airway epithelial cell necroptosis contributes to asthma exacerbation in a mouse model of house dust mite-induced allergic inflammation.


Journal

Mucosal immunology
ISSN: 1935-3456
Titre abrégé: Mucosal Immunol
Pays: United States
ID NLM: 101299742

Informations de publication

Date de publication:
09 2021
Historique:
received: 30 11 2020
accepted: 06 05 2021
revised: 02 05 2021
pubmed: 29 5 2021
medline: 22 1 2022
entrez: 28 5 2021
Statut: ppublish

Résumé

Regulation of epithelial cell death has emerged as a key mechanism controlling immune homeostasis in barrier surfaces. Necroptosis is a type of regulated necrotic cell death induced by receptor interacting protein kinase 3 (RIPK3) that has been shown to cause inflammatory pathologies in different tissues. The role of regulated cell death and particularly necroptosis in lung homeostasis and disease remains poorly understood. Here we show that mice with Airway Epithelial Cell (AEC)-specific deficiency of Fas-associated with death domain (FADD), an adapter essential for caspase-8 activation, developed exacerbated allergic airway inflammation in a mouse model of asthma induced by sensitization and challenge with house dust mite (HDM) extracts. Genetic inhibition of RIPK1 kinase activity by crossing to mice expressing kinase inactive RIPK1 as well as RIPK3 or MLKL deficiency prevented the development of exaggerated HDM-induced asthma pathology in FADD

Identifiants

pubmed: 34045680
doi: 10.1038/s41385-021-00415-5
pii: S1933-0219(22)00210-0
pmc: PMC8379077
doi:

Substances chimiques

Ahr protein, mouse 0
Allergens 0
Basic Helix-Loop-Helix Transcription Factors 0
Biomarkers 0
Fadd protein, mouse 0
Fas-Associated Death Domain Protein 0
Receptors, Aryl Hydrocarbon 0
Immunoglobulin E 37341-29-0
Receptor-Interacting Protein Serine-Threonine Kinases EC 2.7.11.1
Ripk1 protein, mouse EC 2.7.11.1
Ripk3 protein, mouse EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1160-1171

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021. The Author(s).

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Auteurs

Nikos Oikonomou (N)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) & Center for Molecular Medicine, University of Cologne, Cologne, Germany. noikonom@uni-koeln.de.

Martjin J Schuijs (MJ)

Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.

Antonis Chatzigiagkos (A)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) & Center for Molecular Medicine, University of Cologne, Cologne, Germany.

Ariadne Androulidaki (A)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) & Center for Molecular Medicine, University of Cologne, Cologne, Germany.

Vassilis Aidinis (V)

Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece.

Hamida Hammad (H)

Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.

Bart N Lambrecht (BN)

Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.

Manolis Pasparakis (M)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) & Center for Molecular Medicine, University of Cologne, Cologne, Germany. pasparakis@uni-koeln.de.

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