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

Details

Ressource 1Download: 215. Bombaci et al.pdf (3593.75 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_4E57CCCF79FA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
LRR-protein RNH1 dampens the inflammasome activation and is associated with COVID-19 severity.
Journal
Life science alliance
Author(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
Publication state
Published
Issued date
06/2022
Peer-reviewed
Oui
Volume
5
Number
6
Pages
e202101226
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Create date
14/03/2022 8:34
Last modification date
21/11/2022 8:18
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