IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-018-08096-8.html
   My bibliography  Save this article

Breakdown of adaptive immunotolerance induces hepatocellular carcinoma in HBsAg-tg mice

Author

Listed:
  • Lu Zong

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Hui Peng

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Cheng Sun

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Fenglei Li

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Meijuan Zheng

    (The First Affiliated Hospital of Anhui Medical University)

  • Yongyan Chen

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Haiming Wei

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Rui Sun

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Zhigang Tian

    (University of Science and Technology of China
    University of Science and Technology of China)

Abstract

Hepatitis B virus (HBV) can induce chronic inflammation, cirrhosis, and eventually hepatocellular carcinoma (HCC). Despite evidence suggesting a link between adaptive immunity and HBV-related diseases in humans, the immunopathogenic mechanisms involved are seldom described. Here we show that expression of TIGIT, a promising immune checkpoint in tumor immunotherapy, increases with age on hepatic CD8+ T cells in HBsAg-transgenic (HBs-tg) mice whose adaptive immune system is tolerant to HBsAg. TIGIT blockade or deficiency leads to chronic hepatitis and fibrosis, along with the emergence of functional HBsAg-specific cytotoxic T lymphocytes (CTLs), suggesting adaptive immune tolerance could be broken by TIGIT blockade or deficiency. Importantly, HBsAg vaccination further induces nonresolving inflammation and HCC in a CD8+ T cell-dependent manner in TIGIT-blocked or -deficient HBs-tg mice. Therefore, CD8+ T cells play an important role in adaptive immunity-mediated tumor progression and TIGIT is critical in maintenance of liver tolerance by keeping CTLs in homeostatic balance.

Suggested Citation

  • Lu Zong & Hui Peng & Cheng Sun & Fenglei Li & Meijuan Zheng & Yongyan Chen & Haiming Wei & Rui Sun & Zhigang Tian, 2019. "Breakdown of adaptive immunotolerance induces hepatocellular carcinoma in HBsAg-tg mice," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08096-8
    DOI: 10.1038/s41467-018-08096-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-08096-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-08096-8?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_s41467-018-08096-8. 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.