Universität zu Köln

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

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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:	Creators Email ORCID ORCID Put Code Oikonomou, Nikos UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuijs, Martjin J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chatzigiagkos, Antonis UNSPECIFIED UNSPECIFIED UNSPECIFIED Androulidaki, Ariadne UNSPECIFIED UNSPECIFIED UNSPECIFIED Aidinis, Vassilis UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammad, Hamida UNSPECIFIED UNSPECIFIED UNSPECIFIED Lambrecht, Bart N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED
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:	Keywords Language CREOLA BODIES; CASPASE-8; DEATH; HOMEOSTASIS; APOPTOSIS; RELEASE; INTERLEUKIN-1-ALPHA; EXPRESSION; TRIGGERS; IMMUNITY Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58951