Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells.

Autor: Adamik J; Parker Institute for Cancer Immunotherapy, San Francisco, CA, 94129, USA., Munson PV; Parker Institute for Cancer Immunotherapy, San Francisco, CA, 94129, USA., Hartmann FJ; Systems Immunology and Single-Cell Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Combes AJ; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.; CoLabs, University of California San Francisco, San Francisco, CA, USA., Pierre P; Aix Marseille Univ, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Marseille, France.; Institute for Research in Biomedicine (iBiMED) and Ilidio Pinho Foundation, Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal.; Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China., Krummel MF; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA., Bendall SC; Department of Pathology, Stanford University, Palo Alto, CA, 94304, USA., Argüello RJ; Aix Marseille Univ, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Marseille, France. arguello@ciml.univ-mrs.fr., Butterfield LH; Parker Institute for Cancer Immunotherapy, San Francisco, CA, 94129, USA. lbutterfield@parkerici.org.; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA. lbutterfield@parkerici.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Sep 02; Vol. 13 (1), pp. 5184. Date of Electronic Publication: 2022 Sep 02.
DOI: 10.1038/s41467-022-32849-1
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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