IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v563y2018i7733d10.1038_s41586-018-0735-5.html
   My bibliography  Save this article

Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release

Author

Listed:
  • Sho Morioka

    (University of Virginia
    Immunology and Cancer Biology, University of Virginia)

  • Justin S. A. Perry

    (University of Virginia
    Immunology and Cancer Biology, University of Virginia)

  • Michael H. Raymond

    (University of Virginia
    University of Virginia)

  • Christopher B. Medina

    (University of Virginia
    Immunology and Cancer Biology, University of Virginia)

  • Yunlu Zhu

    (University of Virginia)

  • Liyang Zhao

    (University of North Carolina)

  • Vlad Serbulea

    (University of Virginia)

  • Suna Onengut-Gumuscu

    (University of Virginia)

  • Norbert Leitinger

    (University of Virginia)

  • Sarah Kucenas

    (University of Virginia)

  • Jeffrey C. Rathmell

    (Vanderbilt University Medical Center)

  • Liza Makowski

    (University of North Carolina
    University of Tennessee Health Science Center)

  • Kodi S. Ravichandran

    (University of Virginia
    Immunology and Cancer Biology, University of Virginia
    VIB, and Department of Biomedical Molecular Biology)

Abstract

Development and routine tissue homeostasis require a high turnover of apoptotic cells. These cells are removed by professional and non-professional phagocytes via efferocytosis1. How a phagocyte maintains its homeostasis while coordinating corpse uptake, processing ingested materials and secreting anti-inflammatory mediators is incompletely understood1,2. Here, using RNA sequencing to characterize the transcriptional program of phagocytes actively engulfing apoptotic cells, we identify a genetic signature involving 33 members of the solute carrier (SLC) family of membrane transport proteins, in which expression is specifically modulated during efferocytosis, but not during antibody-mediated phagocytosis. We assessed the functional relevance of these SLCs in efferocytic phagocytes and observed a robust induction of an aerobic glycolysis program, initiated by SLC2A1-mediated glucose uptake, with concurrent suppression of the oxidative phosphorylation program. The different steps of phagocytosis2—that is, ‘smell’ (‘find-me’ signals or sensing factors released by apoptotic cells), ‘taste’ (phagocyte–apoptotic cell contact) and ‘ingestion’ (corpse internalization)—activated distinct and overlapping sets of genes, including several SLC genes, to promote glycolysis. SLC16A1 was upregulated after corpse uptake, increasing the release of lactate, a natural by-product of aerobic glycolysis3. Whereas glycolysis within phagocytes contributed to actin polymerization and the continued uptake of corpses, lactate released via SLC16A1 promoted the establishment of an anti-inflammatory tissue environment. Collectively, these data reveal a SLC program that is activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake and show that glycolytic by-products of efferocytosis can influence surrounding cells.

Suggested Citation

  • Sho Morioka & Justin S. A. Perry & Michael H. Raymond & Christopher B. Medina & Yunlu Zhu & Liyang Zhao & Vlad Serbulea & Suna Onengut-Gumuscu & Norbert Leitinger & Sarah Kucenas & Jeffrey C. Rathmell, 2018. "Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release," Nature, Nature, vol. 563(7733), pages 714-718, November.
  • Handle: RePEc:nat:nature:v:563:y:2018:i:7733:d:10.1038_s41586-018-0735-5
    DOI: 10.1038/s41586-018-0735-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-018-0735-5
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-018-0735-5?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Alexandre Gallerand & Bastien Dolfi & Marion I. Stunault & Zakariya Caillot & Alexia Castiglione & Axelle Strazzulla & Chuqiao Chen & Gyu Seong Heo & Hannah Luehmann & Flora Batoul & Nathalie Vaillant, 2024. "Glucose metabolism controls monocyte homeostasis and migration but has no impact on atherosclerosis development in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Tianshi Feng & Xuemei Zhao & Ping Gu & Wah Yang & Cunchuan Wang & Qingyu Guo & Qiaoyun Long & Qing Liu & Ying Cheng & Jin Li & Cynthia Kwan Yui Cheung & Donghai Wu & Xinyu Kong & Yong Xu & Dewei Ye & , 2022. "Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

    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:nature:v:563:y:2018:i:7733:d:10.1038_s41586-018-0735-5. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.