IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34532-x.html
   My bibliography  Save this article

CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses

Author

Listed:
  • Phillip M. Brailey

    (King’s College London
    The Francis Crick Institute)

  • Lauren Evans

    (King’s College London
    The Francis Crick Institute)

  • Juan Carlos López-Rodríguez

    (King’s College London
    The Francis Crick Institute)

  • Anthony Sinadinos

    (King’s College London
    The Francis Crick Institute)

  • Victoria Tyrrel

    (Cardiff University)

  • Gavin Kelly

    (The Francis Crick Institute)

  • Valerie O’Donnell

    (Cardiff University)

  • Peter Ghazal

    (Cardiff University)

  • Susan John

    (King’s College London)

  • Patricia Barral

    (King’s College London
    The Francis Crick Institute)

Abstract

Alterations in cellular metabolism underpin macrophage activation, yet little is known regarding how key immunological molecules regulate metabolic programs in macrophages. Here we uncover a function for the antigen presenting molecule CD1d in the control of lipid metabolism. We show that CD1d-deficient macrophages exhibit a metabolic reprogramming, with a downregulation of lipid metabolic pathways and an increase in exogenous lipid import. This metabolic rewiring primes macrophages for enhanced responses to innate signals, as CD1d-KO cells show higher signalling and cytokine secretion upon Toll-like receptor stimulation. Mechanistically, CD1d modulates lipid import by controlling the internalization of the lipid transporter CD36, while blocking lipid uptake through CD36 restores metabolic and immune responses in macrophages. Thus, our data reveal CD1d as a key regulator of an inflammatory-metabolic circuit in macrophages, independent of its function in the control of T cell responses.

Suggested Citation

  • Phillip M. Brailey & Lauren Evans & Juan Carlos López-Rodríguez & Anthony Sinadinos & Victoria Tyrrel & Gavin Kelly & Valerie O’Donnell & Peter Ghazal & Susan John & Patricia Barral, 2022. "CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34532-x
    DOI: 10.1038/s41467-022-34532-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34532-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-34532-x?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. Jochen Mattner & Kristin L. DeBord & Nahed Ismail & Randal D. Goff & Carlos Cantu & Dapeng Zhou & Pierre Saint-Mezard & Vivien Wang & Ying Gao & Ning Yin & Kasper Hoebe & Olaf Schneewind & David Walke, 2005. "Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections," Nature, Nature, vol. 434(7032), pages 525-529, March.
    2. Gloria Pascual & Alexandra Avgustinova & Stefania Mejetta & Mercè Martín & Andrés Castellanos & Camille Stephan-Otto Attolini & Antoni Berenguer & Neus Prats & Agustí Toll & Juan Antonio Hueto & Coro , 2017. "Targeting metastasis-initiating cells through the fatty acid receptor CD36," Nature, Nature, vol. 541(7635), pages 41-45, January.
    3. Jian-Wei Hao & Juan Wang & Huiling Guo & Yin-Yue Zhao & Hui-Hui Sun & Yi-Fan Li & Xiao-Ying Lai & Ning Zhao & Xu Wang & Changchuan Xie & Lixin Hong & Xi Huang & Hong-Rui Wang & Cheng-Bin Li & Bin Lian, 2020. "CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    4. Torsten Olszak & Joana F. Neves & C. Marie Dowds & Kristi Baker & Jonathan Glickman & Nicholas O. Davidson & Chyuan-Sheng Lin & Christian Jobin & Stephan Brand & Karl Sotlar & Koichiro Wada & Kazufumi, 2014. "Protective mucosal immunity mediated by epithelial CD1d and IL-10," Nature, Nature, vol. 509(7501), pages 497-502, May.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Amy Dawson & Martha M. Zarou & Bodhayan Prasad & Joana Bittencourt-Silvestre & Désirée Zerbst & Ekaterini Himonas & Ya-Ching Hsieh & Isabel Loon & Giovanny Rodriguez Blanco & Angela Ianniciello & Zsom, 2024. "Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    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. Graham A. Heieis & Thiago A. Patente & Luís Almeida & Frank Vrieling & Tamar Tak & Georgia Perona-Wright & Rick M. Maizels & Rinke Stienstra & Bart Everts, 2023. "Metabolic heterogeneity of tissue-resident macrophages in homeostasis and during helminth infection," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Channakeshava Sokke Umeshappa & Patricia Solé & Jun Yamanouchi & Saswat Mohapatra & Bas G. J. Surewaard & Josep Garnica & Santiswarup Singha & Debajyoti Mondal & Elena Cortés-Vicente & Charlotte D’Mel, 2022. "Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic and diabetogenic autoimmunity," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. Yanjie Tan & Zhenzhou Huang & Yi Jin & Jiaying Wang & Hongjun Fan & Yangyang Liu & Liang Zhang & Yue Wu & Peiwei Liu & Tianliang Li & Jie Ran & He Tian & Sin Man Lam & Min Liu & Jun Zhou & Yunfan Yang, 2024. "Lipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Ping Yang & Hong Qin & Yiyu Li & Anhua Xiao & Enze Zheng & Han Zeng & Chunxiao Su & Xiaoqing Luo & Qiannan Lu & Meng Liao & Lei Zhao & Li Wei & Zac Varghese & John F. Moorhead & Yaxi Chen & Xiong Z. R, 2022. "CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. C. Megan Young & Laurent Beziaud & Pierre Dessen & Angela Madurga Alonso & Albert Santamaria-Martínez & Joerg Huelsken, 2023. "Metabolic dependencies of metastasis-initiating cells in female breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Ondrej Suchanek & John R. Ferdinand & Zewen K. Tuong & Sathi Wijeyesinghe & Anita Chandra & Ann-Katrin Clauder & Larissa N. Almeida & Simon Clare & Katherine Harcourt & Christopher J. Ward & Rachael B, 2023. "Tissue-resident B cells orchestrate macrophage polarisation and function," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    7. Jan Philipp Menzel & Reuben S. E. Young & Aurélie H. Benfield & Julia S. Scott & Puttandon Wongsomboon & Lukáš Cudlman & Josef Cvačka & Lisa M. Butler & Sónia T. Henriques & Berwyck L. J. Poad & Steph, 2023. "Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Shao-Chin Wu & Yuan-Ming Lo & Jui-Hao Lee & Chin-Yau Chen & Tung-Wei Chen & Hong-Wen Liu & Wei-Nan Lian & Kate Hua & Chen-Chung Liao & Wei-Ju Lin & Chih-Yung Yang & Chien-Yi Tung & Chi-Hung Lin, 2022. "Stomatin modulates adipogenesis through the ERK pathway and regulates fatty acid uptake and lipid droplet growth," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Li Weng & Wen-Shuai Tang & Xu Wang & Yingyun Gong & Changqin Liu & Ni-Na Hong & Ying Tao & Kuang-Zheng Li & Shu-Ning Liu & Wanzi Jiang & Ying Li & Ke Yao & Li Chen & He Huang & Yu-Zheng Zhao & Ze-Ping, 2024. "Surplus fatty acid synthesis increases oxidative stress in adipocytes and induces lipodystrophy," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. Daniela Michelatti & Sven Beyes & Chiara Bernardis & Maria Luce Negri & Leonardo Morelli & Naiara Garcia Bediaga & Vittoria Poli & Luca Fagnocchi & Sara Lago & Sarah D’Annunzio & Nicole Cona & Ilaria , 2024. "Oncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting transcriptional memory," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    11. Yuying Tan & Junjie Li & Guangyuan Zhao & Kai-Chih Huang & Horacio Cardenas & Yinu Wang & Daniela Matei & Ji-Xin Cheng, 2022. "Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. V. S. Peche & T. A. Pietka & M. Jacome-Sosa & D. Samovski & H. Palacios & G. Chatterjee-Basu & A. C. Dudley & W. Beatty & G. A. Meyer & I. J. Goldberg & N. A. Abumrad, 2023. "Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    13. Rens Peeters & Jorge Cuenca-Escalona & Esther A. Zaal & Anna T. Hoekstra & Anouk C. G. Balvert & Marcos Vidal-Manrique & Niek Blomberg & Sjoerd J. Deventer & Rinke Stienstra & Julia Jellusova & Martin, 2022. "Fatty acid metabolism in aggressive B-cell lymphoma is inhibited by tetraspanin CD37," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    14. Norimasa Iwanami & Andreas S. Richter & Katarzyna Sikora & Thomas Boehm, 2023. "Tnpo3 controls splicing of the pre-mRNA encoding the canonical TCR α chain of iNKT cells," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    15. Ling Tao & Mahmoud A. Mohammad & Giorgio Milazzo & Myrthala Moreno-Smith & Tajhal D. Patel & Barry Zorman & Andrew Badachhape & Blanca E. Hernandez & Amber B. Wolf & Zihua Zeng & Jennifer H. Foster & , 2022. "MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    16. Jian Xiao & Le-Wei Dong & Shuai Liu & Fan-Hua Meng & Chang Xie & Xiao-Yi Lu & Weiping J. Zhang & Jie Luo & Bao-Liang Song, 2023. "Bile acids-mediated intracellular cholesterol transport promotes intestinal cholesterol absorption and NPC1L1 recycling," Nature Communications, Nature, vol. 14(1), pages 1-16, 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_s41467-022-34532-x. 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.