IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32849-1.html
   My bibliography  Save this article

Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells

Author

Listed:
  • 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
    University of California San Francisco
    CoLabs, University of California San Francisco)

  • Philippe Pierre

    (Centre d’Immunologie de Marseille-Luminy
    University of Aveiro
    Shanghai Jiao Tong University School of Medicine)

  • Matthew F. Krummel

    (University of California San Francisco
    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
    University of California San Francisco)

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.

Suggested Citation

  • Juraj Adamik & Paul V. Munson & Felix J. Hartmann & Alexis J. Combes & Philippe Pierre & Matthew F. Krummel & Sean C. Bendall & Rafael J. Argüello & Lisa H. Butterfield, 2022. "Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32849-1
    DOI: 10.1038/s41467-022-32849-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32849-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32849-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Erika M. Palmieri & Marieli Gonzalez-Cotto & Walter A. Baseler & Luke C. Davies & Bart Ghesquière & Nunziata Maio & Christopher M. Rice & Tracey A. Rouault & Teresa Cassel & Richard M. Higashi & Andre, 2020. "Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    2. Xingrong Du & Jing Wen & Yanyan Wang & Peer W. F. Karmaus & Alireza Khatamian & Haiyan Tan & Yuxin Li & Cliff Guy & Thanh-Long M. Nguyen & Yogesh Dhungana & Geoffrey Neale & Junmin Peng & Jiyang Yu & , 2018. "Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells," Nature, Nature, vol. 558(7708), pages 141-145, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Lucía López & Luciano Gastón Morosi & Federica Terza & Pierre Bourdely & Giuseppe Rospo & Roberto Amadio & Giulia Maria Piperno & Valentina Russo & Camilla Volponi & Simone Vodret & Sonal Joshi & Fran, 2024. "Dendritic cell-targeted therapy expands CD8 T cell responses to bona-fide neoantigens in lung tumors," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Hayden T. Pacl & Krishna C. Chinta & Vineel P. Reddy & Sajid Nadeem & Ritesh R. Sevalkar & Kievershen Nargan & Kapongo Lumamba & Threnesan Naidoo & Joel N. Glasgow & Anupam Agarwal & Adrie J. C. Steyn, 2023. "NAD(H) homeostasis underlies host protection mediated by glycolytic myeloid cells in tuberculosis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Erika M. Palmieri & Ronald Holewinski & Christopher L. McGinity & Ciro L. Pierri & Nunziata Maio & Jonathan M. Weiss & Vincenzo Tragni & Katrina M. Miranda & Tracey A. Rouault & Thorkell Andresson & D, 2023. "Pyruvate dehydrogenase operates as an intramolecular nitroxyl generator during macrophage metabolic reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    4. Jiajia Wang & Jiaying Wang & Wenxiang Hong & Lulu Zhang & Liqian Song & Qi Shi & Yanfei Shao & Guifeng Hao & Chunyan Fang & Yueping Qiu & Lijun Yang & Zhaoxu Yang & Jincheng Wang & Ji Cao & Bo Yang & , 2021. "Optineurin modulates the maturation of dendritic cells to regulate autoimmunity through JAK2-STAT3 signaling," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    5. Guihong Lu & Xiaojun Wang & Feng Li & Shuang Wang & Jiawei Zhao & Jinyi Wang & Jing Liu & Chengliang Lyu & Peng Ye & Hui Tan & Weiping Li & Guanghui Ma & Wei Wei, 2022. "Engineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Juraj Adamik & Paul V. Munson & Deena M. Maurer & Felix J. Hartmann & Sean C. Bendall & Rafael J. Argüello & Lisa H. Butterfield, 2023. "Immuno-metabolic dendritic cell vaccine signatures associate with overall survival in vaccinated melanoma patients," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    7. Xinran Dong & Liang Ding & Andrew Thrasher & Xinge Wang & Jingjing Liu & Qingfei Pan & Jordan Rash & Yogesh Dhungana & Xu Yang & Isabel Risch & Yuxin Li & Lei Yan & Michael Rusch & Clay McLeod & Koon-, 2023. "NetBID2 provides comprehensive hidden driver analysis," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32849-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.