Interleukin-10 Prevents Pathological Microglia Hyperactivation following Peripheral Endotoxin Challenge.
Cx3cr1
IL-10
LPS
LTP
Microglia activation
TNF
conditional mutagenesis
sepsis
sickness behavior
tamoxifen
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
17 11 2020
17 11 2020
Historique:
received:
17
01
2020
revised:
06
08
2020
accepted:
23
09
2020
pubmed:
14
10
2020
medline:
1
5
2021
entrez:
13
10
2020
Statut:
ppublish
Résumé
Microglia, the resident macrophages of the brain parenchyma, are key players in central nervous system (CNS) development, homeostasis, and disorders. Distinct brain pathologies seem associated with discrete microglia activation modules. How microglia regain quiescence following challenges remains less understood. Here, we explored the role of the interleukin-10 (IL-10) axis in restoring murine microglia homeostasis following a peripheral endotoxin challenge. Specifically, we show that lipopolysaccharide (LPS)-challenged mice harboring IL-10 receptor-deficient microglia displayed neuronal impairment and succumbed to fatal sickness. Addition of a microglial tumor necrosis factor (TNF) deficiency rescued these animals, suggesting a microglia-based circuit driving pathology. Single cell transcriptome analysis revealed various IL-10 producing immune cells in the CNS, including most prominently Ly49D
Identifiants
pubmed: 33049219
pii: S1074-7613(20)30412-X
doi: 10.1016/j.immuni.2020.09.018
pii:
doi:
Substances chimiques
Biomarkers
0
Endotoxins
0
IL10 protein, mouse
0
Lipopolysaccharides
0
Interleukin-10
130068-27-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1033-1049.e7Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare that they have no competing interests.