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Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440236/ https://www.ncbi.nlm.nih.gov/pubmed/36056019 http://dx.doi.org/10.1038/s41467-022-32849-1 |
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author | Adamik, Juraj Munson, Paul V. Hartmann, Felix J. Combes, Alexis J. Pierre, Philippe Krummel, Matthew F. Bendall, Sean C. Argüello, Rafael J. Butterfield, Lisa H. |
author_facet | Adamik, Juraj Munson, Paul V. Hartmann, Felix J. Combes, Alexis J. Pierre, Philippe Krummel, Matthew F. Bendall, Sean C. Argüello, Rafael J. Butterfield, Lisa H. |
author_sort | Adamik, Juraj |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9440236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-94402362022-09-04 Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells Adamik, Juraj Munson, Paul V. Hartmann, Felix J. Combes, Alexis J. Pierre, Philippe Krummel, Matthew F. Bendall, Sean C. Argüello, Rafael J. Butterfield, Lisa H. Nat Commun Article 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. Nature Publishing Group UK 2022-09-02 /pmc/articles/PMC9440236/ /pubmed/36056019 http://dx.doi.org/10.1038/s41467-022-32849-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Adamik, Juraj Munson, Paul V. Hartmann, Felix J. Combes, Alexis J. Pierre, Philippe Krummel, Matthew F. Bendall, Sean C. Argüello, Rafael J. Butterfield, Lisa H. Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells |
title | Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells |
title_full | Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells |
title_fullStr | Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells |
title_full_unstemmed | Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells |
title_short | Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells |
title_sort | distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440236/ https://www.ncbi.nlm.nih.gov/pubmed/36056019 http://dx.doi.org/10.1038/s41467-022-32849-1 |
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