Back to Search Start Over

Epithelial Nlrp10 inflammasome mediates protection against intestinal autoinflammation.

Authors :
Zheng D
Mohapatra G
Kern L
He Y
Shmueli MD
Valdés-Mas R
Kolodziejczyk AA
Próchnicki T
Vasconcelos MB
Schorr L
Hertel F
Lee YS
Rufino MC
Ceddaha E
Shimshy S
Hodgetts RJ
Dori-Bachash M
Kleimeyer C
Goldenberg K
Heinemann M
Stettner N
Harmelin A
Shapiro H
Puschhof J
Chen M
Flavell RA
Latz E
Merbl Y
Abdeen SK
Elinav E
Source :
Nature immunology [Nat Immunol] 2023 Apr; Vol. 24 (4), pp. 585-594. Date of Electronic Publication: 2023 Mar 20.
Publication Year :
2023

Abstract

Unlike other nucleotide oligomerization domain-like receptors, Nlrp10 lacks a canonical leucine-rich repeat domain, suggesting that it is incapable of signal sensing and inflammasome formation. Here we show that mouse Nlrp10 is expressed in distal colonic intestinal epithelial cells (IECs) and modulated by the intestinal microbiome. In vitro, Nlrp10 forms an Apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)-dependent, m-3M3FBS-activated, polyinosinic:polycytidylic acid-modulated inflammasome driving interleukin-1β and interleukin-18 secretion. In vivo, Nlrp10 signaling is dispensable during steady state but becomes functional during autoinflammation in antagonizing mucosal damage. Importantly, whole-body or conditional IEC Nlrp10 depletion leads to reduced IEC caspase-1 activation, coupled with enhanced susceptibility to dextran sodium sulfate-induced colitis, mediated by altered inflammatory and healing programs. Collectively, understanding Nlrp10 inflammasome-dependent and independent activity, regulation and possible human relevance might facilitate the development of new innate immune anti-inflammatory interventions.<br /> (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Details

Language :
English
ISSN :
1529-2916
Volume :
24
Issue :
4
Database :
MEDLINE
Journal :
Nature immunology
Publication Type :
Academic Journal
Accession number :
36941399
Full Text :
https://doi.org/10.1038/s41590-023-01450-z