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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
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    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.

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