Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells

Juraj Adamik, Paul V. Munson, Felix J. Hartmann, Alexis J. Combes, Philippe Pierre, Matthew F. Krummel, Sean C. Bendall, Rafael J. Argüello () and Lisa H. Butterfield ()
Additional contact information
Juraj Adamik: Parker Institute for Cancer Immunotherapy
Paul V. Munson: Parker Institute for Cancer Immunotherapy
Felix J. Hartmann: German Cancer Research Center (DKFZ)
Alexis J. Combes: University of California San Francisco
Philippe Pierre: Centre d’Immunologie de Marseille-Luminy
Matthew F. Krummel: University of California San Francisco
Sean C. Bendall: Stanford University
Rafael J. Argüello: Centre d’Immunologie de Marseille-Luminy
Lisa H. Butterfield: Parker Institute for Cancer Immunotherapy

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32849-1

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DOI: 10.1038/s41467-022-32849-1

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