Oikonomou, Nikos, Schuijs, Martjin J., Chatzigiagkos, Antonis, Androulidaki, Ariadne, Aidinis, Vassilis, Hammad, Hamida, Lambrecht, Bart N. and Pasparakis, Manolis ORCID: 0000-0002-9870-0966 (2021). Airway epithelial cell necroptosis contributes to asthma exacerbation in a mouse model of house dust mite-induced allergic inflammation. Mucosal Immunol., 14 (5). S. 1160 - 1172. LONDON: SPRINGERNATURE. ISSN 1935-3456

Full text not available from this repository.

Abstract

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(AEC-KO) mice, suggesting that necroptosis of FADD-deficient AECs augmented the allergic immune response. These results reveal a role of AEC necroptosis in amplifying airway allergic inflammation and suggest that necroptosis could contribute to asthma exacerbations caused by respiratory virus infections inducing AEC death.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Oikonomou, NikosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuijs, Martjin J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chatzigiagkos, AntonisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Androulidaki, AriadneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aidinis, VassilisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hammad, HamidaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lambrecht, Bart N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
URN: urn:nbn:de:hbz:38-589511
DOI: 10.1038/s41385-021-00415-5
Journal or Publication Title: Mucosal Immunol.
Volume: 14
Number: 5
Page Range: S. 1160 - 1172
Date: 2021
Publisher: SPRINGERNATURE
Place of Publication: LONDON
ISSN: 1935-3456
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CREOLA BODIES; CASPASE-8; DEATH; HOMEOSTASIS; APOPTOSIS; RELEASE; INTERLEUKIN-1-ALPHA; EXPRESSION; TRIGGERS; IMMUNITYMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/58951

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item