IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-10335-5.html
   My bibliography  Save this article

Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition

Author

Listed:
  • Branca I. Pereira

    (University College London)

  • Oliver P. Devine

    (University College London)

  • Milica Vukmanovic-Stejic

    (University College London)

  • Emma S. Chambers

    (University College London)

  • Priya Subramanian

    (University College London)

  • Neil Patel

    (University College London)

  • Alex Virasami

    (Great Ormond Street Hospital for Children, University College London)

  • Neil J. Sebire

    (Great Ormond Street Hospital for Children, University College London)

  • Veronica Kinsler

    (Great Ormond Street Hospital for Children, University College London)

  • Alexis Valdovinos

    (Buck Institute for Research on Aging)

  • Claude Jourdan LeSaux

    (Buck Institute for Research on Aging)

  • João F. Passos

    (Institute for Cell and Molecular Biosciences & Newcastle University Institute for Ageing
    Mayo Clinic)

  • Antony Antoniou

    (Faculty of Health and Life Sciences, Northumbria University)

  • Malcom H. A. Rustin

    (University College London)

  • Judith Campisi

    (Buck Institute for Research on Aging
    Lawrence Berkeley National Laboratory)

  • Arne N. Akbar

    (University College London)

Abstract

Senescent cells accumulate in human tissues during ageing and contribute to age-related pathologies. The mechanisms responsible for their accumulation are unclear. Here we show that senescent dermal fibroblasts express the non-classical MHC molecule HLA-E, which interacts with the inhibitory receptor NKG2A expressed by NK and highly differentiated CD8+ T cells to inhibit immune responses against senescent cells. HLA-E expression is induced by senescence-associated secretary phenotype-related pro-inflammatory cytokines, and is regulated by p38 MAP kinase signalling in vitro. Consistently, HLA-E expression is increased on senescent cells in human skin sections from old individuals, when compared with those from young, and in human melanocytic nevi relative to normal skin. Lastly, blocking the interaction between HLA-E and NKG2A boosts immune responses against senescent cells in vitro. We thus propose that increased HLA-E expression contributes to persistence of senescent cells in tissues, thereby suggesting a new strategy for eliminating senescent cells during ageing.

Suggested Citation

  • Branca I. Pereira & Oliver P. Devine & Milica Vukmanovic-Stejic & Emma S. Chambers & Priya Subramanian & Neil Patel & Alex Virasami & Neil J. Sebire & Veronica Kinsler & Alexis Valdovinos & Claude Jou, 2019. "Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10335-5
    DOI: 10.1038/s41467-019-10335-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-10335-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-10335-5?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
    ---><---

    Citations

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


    Cited by:

    1. Sumin Jo & Shipra Das & Alan Williams & Anne-Sophie Chretien & Thomas Pagliardini & Aude Roy & Jorge Postigo Fernandez & Diane Clerre & Billal Jahangiri & Isabelle Chion-Sotinel & Sandra Rozlan & Emil, 2022. "Endowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing," Nature Communications, Nature, vol. 13(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:10:y:2019:i:1:d:10.1038_s41467-019-10335-5. 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.