Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 09 2022
02 09 2022
Historique:
received:
15
10
2021
accepted:
20
08
2022
entrez:
2
9
2022
pubmed:
3
9
2022
medline:
9
9
2022
Statut:
epublish
Résumé
Cellular metabolism underpins immune cell functionality, yet our understanding of metabolic influences in human dendritic cell biology and their ability to orchestrate immune responses is poorly developed. Here, we map single-cell metabolic states and immune profiles of inflammatory and tolerogenic monocytic dendritic cells using recently developed multiparametric approaches. Single-cell metabolic pathway activation scores reveal simultaneous engagement of multiple metabolic pathways in distinct monocytic dendritic cell differentiation stages. GM-CSF/IL4-induce rapid reprogramming of glycolytic monocytes and transient co-activation of mitochondrial pathways followed by TLR4-dependent maturation of dendritic cells. Skewing of the mTOR:AMPK phosphorylation balance and upregulation of OXPHOS, glycolytic and fatty acid oxidation metabolism underpin metabolic hyperactivity and an immunosuppressive phenotype of tolerogenic dendritic cells, which exhibit maturation-resistance and a de-differentiated immune phenotype marked by unique immunoregulatory receptor signatures. This single-cell dataset provides important insights into metabolic pathways impacting the immune profiles of human dendritic cells.
Identifiants
pubmed: 36056019
doi: 10.1038/s41467-022-32849-1
pii: 10.1038/s41467-022-32849-1
pmc: PMC9440236
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5184Subventions
Organisme : NCI NIH HHS
ID : R01 CA197363
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063720
Pays : United States
Organisme : NIH HHS
ID : S10 OD026940
Pays : United States
Informations de copyright
© 2022. The Author(s).
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