Cellular and transcriptional dynamics of human neutrophils at steady state and upon stress.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
26
11
2021
accepted:
10
08
2022
pubmed:
23
9
2022
medline:
13
10
2022
entrez:
22
9
2022
Statut:
ppublish
Résumé
Traditionally viewed as poorly plastic, neutrophils are now recognized as functionally diverse; however, the extent and determinants of neutrophil heterogeneity in humans remain unclear. We performed a comprehensive immunophenotypic and transcriptome analysis, at a bulk and single-cell level, of neutrophils from healthy donors and patients undergoing stress myelopoiesis upon exposure to growth factors, transplantation of hematopoietic stem cells (HSC-T), development of pancreatic cancer and viral infection. We uncover an extreme diversity of human neutrophils in vivo, reflecting the rates of cell mobilization, differentiation and exposure to environmental signals. Integrated control of developmental and inducible transcriptional programs linked flexible granulopoietic outputs with elicitation of stimulus-specific functional responses. In this context, we detected an acute interferon (IFN) response in the blood of patients receiving HSC-T that was mirrored by marked upregulation of IFN-stimulated genes in neutrophils but not in monocytes. Systematic characterization of human neutrophil plasticity may uncover clinically relevant biomarkers and support the development of diagnostic and therapeutic tools.
Identifiants
pubmed: 36138183
doi: 10.1038/s41590-022-01311-1
pii: 10.1038/s41590-022-01311-1
pmc: PMC7615267
mid: EMS152526
doi:
Substances chimiques
Biomarkers
0
Plastics
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1470-1483Informations de copyright
© 2022. Springer Nature America, Inc.
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