IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12730.html
   My bibliography  Save this article

NK cell development requires Tsc1-dependent negative regulation of IL-15-triggered mTORC1 activation

Author

Listed:
  • Meixiang Yang

    (Institute for Immunology and School of Medicine, Tsinghua University
    Biomedical Translational Research Institute, Jinan University)

  • Shasha Chen

    (Institute for Immunology and School of Medicine, Tsinghua University)

  • Juan Du

    (Institute for Immunology and School of Medicine, Tsinghua University)

  • Junming He

    (Biomedical Translational Research Institute, Jinan University)

  • Yuande Wang

    (Biomedical Translational Research Institute, Jinan University)

  • Zehua Li

    (Institute for Immunology and School of Medicine, Tsinghua University)

  • Guangao Liu

    (Biomedical Translational Research Institute, Jinan University)

  • Wanwen Peng

    (Biomedical Translational Research Institute, Jinan University)

  • Xiaokang Zeng

    (Biomedical Translational Research Institute, Jinan University)

  • Dan Li

    (Institute for Immunology and School of Medicine, Tsinghua University)

  • Panglian Xu

    (School of Medicine, Tsinghua University)

  • Wei Guo

    (School of Medicine, Tsinghua University)

  • Zai Chang

    (Center of Animal Facility, Tsinghua University)

  • Song Wang

    (Collaborative Innovation Center, Wuhan Sports University)

  • Zhigang Tian

    (School of Life Sciences, University of Sciences and Technology of China)

  • Zhongjun Dong

    (Institute for Immunology and School of Medicine, Tsinghua University)

Abstract

Activation of metabolic signalling by IL-15 is required for natural killer (NK) cell development. Here we show that Tsc1, a repressor of mTOR, is dispensable for the terminal maturation, survival and function of NK cells but is critical to restrict exhaustive proliferation of immature NK cells and activation downstream of IL-15 during NK cell development. Tsc1 is expressed in immature NK cells and is upregulated by IL-15. Haematopoietic-specific deletion of Tsc1 causes a marked decrease in the number of NK cells and compromises rejection of ‘missing-self’ haematopoietic tumours and allogeneic bone marrow. The residual Tsc1-null NK cells display activated, pro-apoptotic phenotype and elevated mTORC1 activity. Deletion of Raptor, a component of mTORC1, largely reverses these defects. Tsc1-deficient NK cells express increased levels of T-bet and downregulate Eomes and CD122, a subunit of IL-15 receptor. These results reveal a role for Tsc1-dependent inhibition of mTORC1 activation during immature NK cell development.

Suggested Citation

  • Meixiang Yang & Shasha Chen & Juan Du & Junming He & Yuande Wang & Zehua Li & Guangao Liu & Wanwen Peng & Xiaokang Zeng & Dan Li & Panglian Xu & Wei Guo & Zai Chang & Song Wang & Zhigang Tian & Zhongj, 2016. "NK cell development requires Tsc1-dependent negative regulation of IL-15-triggered mTORC1 activation," Nature Communications, Nature, vol. 7(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12730
    DOI: 10.1038/ncomms12730
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12730
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12730?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
    ---><---

    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:7:y:2016:i:1:d:10.1038_ncomms12730. 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.