IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-11895-2.html
   My bibliography  Save this article

Caspase-11 signaling enhances graft-versus-host disease

Author

Listed:
  • Yanyan Lu

    (Central South University)

  • Ran Meng

    (Central South University)

  • Xiangyu Wang

    (Central South University)

  • Yajing Xu

    (Central South University)

  • Yiting Tang

    (Central South University)

  • Jianfeng Wu

    (Xiamen University)

  • Qianqian Xue

    (Central South University)

  • Songlin Yu

    (Central South University)

  • Mingwu Duan

    (Central South University)

  • Dongyong Shan

    (Central South University)

  • Qingde Wang

    (University of Pittsburgh Medical Center)

  • Haichao Wang

    (Northwell Health)

  • Timothy R. Billiar

    (University of Pittsburgh Medical Center)

  • Xianzhong Xiao

    (Central South University
    Central South University)

  • Fangping Chen

    (Central South University)

  • Ben Lu

    (Central South University
    Central South University
    Central South University)

Abstract

Acute graft-versus-host disease (GVHD) remains a major obstacle for the wider usage of allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is an effective therapy for hematopoietic malignancy. Here we show that caspase-11, the cytosolic receptor for bacterial endotoxin (lipopolysaccharide: LPS), enhances GVHD severity. Allo-HSCT markedly increases the LPS-caspase-11 interaction, leading to the cleavage of gasdermin D (GSDMD). Caspase-11 and GSDMD mediate the release of interleukin-1α (IL-1α) in allo-HSCT. Deletion of Caspase-11 or Gsdmd, inhibition of LPS-caspase-11 interaction, or neutralizing IL-1α uniformly reduces intestinal inflammation, tissue damage, donor T cell expansion and mortality in allo-HSCT. Importantly, Caspase-11 deficiency does not decrease the graft-versus-leukemia (GVL) activity, which is essential to prevent cancer relapse. These findings have major implications for allo-HSCT, as pharmacological interference with the caspase-11 signaling might reduce GVHD while preserving GVL activity.

Suggested Citation

  • Yanyan Lu & Ran Meng & Xiangyu Wang & Yajing Xu & Yiting Tang & Jianfeng Wu & Qianqian Xue & Songlin Yu & Mingwu Duan & Dongyong Shan & Qingde Wang & Haichao Wang & Timothy R. Billiar & Xianzhong Xiao, 2019. "Caspase-11 signaling enhances graft-versus-host disease," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11895-2
    DOI: 10.1038/s41467-019-11895-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-11895-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-11895-2?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:10:y:2019:i:1:d:10.1038_s41467-019-11895-2. 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.