LRR-protein RNH1 dampens the inflammasome activation and is associated with COVID-19 severity.

Détails

Ressource 1Télécharger: 215. Bombaci et al.pdf (3593.75 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_4E57CCCF79FA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
LRR-protein RNH1 dampens the inflammasome activation and is associated with COVID-19 severity.
Périodique
Life science alliance
Auteur⸱e⸱s
Bombaci G., Sarangdhar M.A., Andina N., Tardivel A., Yu E.C., Mackie G.M., Pugh M., Ozan V.B., Banz Y., Spinetti T., Hirzel C., Youd E., Schefold J.C., Taylor G., Gazdhar A., Bonadies N., Angelillo-Scherrer A., Schneider P., Maslowski K.M., Allam R.
ISSN
2575-1077 (Electronic)
ISSN-L
2575-1077
Statut éditorial
Publié
Date de publication
06/2022
Peer-reviewed
Oui
Volume
5
Numéro
6
Pages
e202101226
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Inflammasomes are cytosolic innate immune sensors of pathogen infection and cellular damage that induce caspase-1-mediated inflammation upon activation. Although inflammation is protective, uncontrolled excessive inflammation can cause inflammatory diseases and can be detrimental, such as in coronavirus disease (COVID-19). However, the underlying mechanisms that control inflammasome activation are incompletely understood. Here we report that the leucine-rich repeat (LRR) protein ribonuclease inhibitor (RNH1), which shares homology with LRRs of NLRP (nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing) proteins, attenuates inflammasome activation. Deletion of RNH1 in macrophages increases interleukin (IL)-1β production and caspase-1 activation in response to inflammasome stimulation. Mechanistically, RNH1 decreases pro-IL-1β expression and induces proteasome-mediated caspase-1 degradation. Corroborating this, mouse models of monosodium urate (MSU)-induced peritonitis and lipopolysaccharide (LPS)-induced endotoxemia, which are dependent on caspase-1, respectively, show increased neutrophil infiltration and lethality in Rnh1 <sup>-/-</sup> mice compared with wild-type mice. Furthermore, RNH1 protein levels were negatively related with disease severity and inflammation in hospitalized COVID-19 patients. We propose that RNH1 is a new inflammasome regulator with relevance to COVID-19 severity.
Mots-clé
Animals, COVID-19/immunology, COVID-19/pathology, Carrier Proteins/metabolism, Caspase 1/metabolism, Humans, Inflammasomes/metabolism, Leucine-Rich Repeat Proteins/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B/metabolism, NLR Family, Pyrin Domain-Containing 3 Protein/metabolism, Patient Acuity, Proteasome Endopeptidase Complex/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/03/2022 8:34
Dernière modification de la notice
21/11/2022 8:18
Données d'usage