Co-option of Neutrophil Fates by Tissue Environments.
Animals
Cell Lineage
Chromatin
/ metabolism
Female
Hematopoiesis
Intestines
/ blood supply
Lung
/ blood supply
Male
Mice, Inbred C57BL
Neovascularization, Physiologic
Neutrophils
/ metabolism
Nuclear Receptor Subfamily 4, Group A, Member 1
/ metabolism
Organ Specificity
Receptors, CXCR4
/ metabolism
Single-Cell Analysis
Transcription, Genetic
Transcriptome
/ genetics
angiogenesis
immune heterogeneity
immune niche
innate immunity
neutrophil lifespan
neutrophils
single-cell analysis
tissue-resident cells
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
25 11 2020
25 11 2020
Historique:
received:
10
01
2020
revised:
10
08
2020
accepted:
01
10
2020
pubmed:
26
10
2020
medline:
20
5
2021
entrez:
25
10
2020
Statut:
ppublish
Résumé
Classically considered short-lived and purely defensive leukocytes, neutrophils are unique in their fast and moldable response to stimulation. This plastic behavior may underlie variable and even antagonistic functions during inflammation or cancer, yet the full spectrum of neutrophil properties as they enter healthy tissues remains unexplored. Using a new model to track neutrophil fates, we found short but variable lifetimes across multiple tissues. Through analysis of the receptor, transcriptional, and chromatin accessibility landscapes, we identify varying neutrophil states and assign non-canonical functions, including vascular repair and hematopoietic homeostasis. Accordingly, depletion of neutrophils compromised angiogenesis during early age, genotoxic injury, and viral infection, and impaired hematopoietic recovery after irradiation. Neutrophils acquired these properties in target tissues, a process that, in the lungs, occurred in CXCL12-rich areas and relied on CXCR4. Our results reveal that tissues co-opt neutrophils en route for elimination to induce programs that support their physiological demands.
Identifiants
pubmed: 33098771
pii: S0092-8674(20)31309-X
doi: 10.1016/j.cell.2020.10.003
pii:
doi:
Substances chimiques
Chromatin
0
NR4A1 protein, human
0
Nuclear Receptor Subfamily 4, Group A, Member 1
0
Receptors, CXCR4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1282-1297.e18Subventions
Organisme : Versus Arthritis
ID : 20892
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.