IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-44390-w.html
   My bibliography  Save this article

p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome

Author

Listed:
  • Jianming Wang

    (Rutgers University)

  • Chun-Yuan Chang

    (Rutgers University)

  • Xue Yang

    (Rutgers University)

  • Fan Zhou

    (Rutgers University)

  • Juan Liu

    (Rutgers University)

  • Jill Bargonetti

    (Hunter College, City University of New York)

  • Lanjing Zhang

    (Rutgers University
    Rutgers University
    Penn Medicine Princeton Medical Center)

  • Ping Xie

    (Rutgers University
    Rutgers University)

  • Zhaohui Feng

    (Rutgers University)

  • Wenwei Hu

    (Rutgers University)

Abstract

Radiation-induced gastrointestinal syndrome is a major complication and limiting factor for radiotherapy. Tumor suppressor p53 has a protective role in radiation-induced gastrointestinal toxicity. However, its underlying mechanism remains unclear. Here we report that regulating the IL12-p40/MHC class II signaling pathway is a critical mechanism by which p53 protects against radiation-induced gastrointestinal syndrome. p53 inhibits the expression of inflammatory cytokine IL12-p40, which in turn suppresses the expression of MHC class II on intestinal epithelial cells to suppress T cell activation and inflammation post-irradiation that causes intestinal stem cell damage. Anti-IL12-p40 neutralizing antibody inhibits inflammation and rescues the defects in intestinal epithelial regeneration post-irradiation in p53-deficient mice and prolongs mouse survival. These results uncover that the IL12-p40/MHC class II signaling mediates the essential role of p53 in ensuring intestinal stem cell function and proper immune reaction in response to radiation to protect mucosal epithelium, and suggest a potential therapeutic strategy to protect against radiation-induced gastrointestinal syndrome.

Suggested Citation

  • Jianming Wang & Chun-Yuan Chang & Xue Yang & Fan Zhou & Juan Liu & Jill Bargonetti & Lanjing Zhang & Ping Xie & Zhaohui Feng & Wenwei Hu, 2024. "p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44390-w
    DOI: 10.1038/s41467-023-44390-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44390-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44390-w?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
    ---><---

    References listed on IDEAS

    as
    1. Eliran Kadosh & Irit Snir-Alkalay & Avanthika Venkatachalam & Shahaf May & Audrey Lasry & Ela Elyada & Adar Zinger & Maya Shaham & Gitit Vaalani & Marco Mernberger & Thorsten Stiewe & Eli Pikarsky & M, 2020. "The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic," Nature, Nature, vol. 586(7827), pages 133-138, October.
    2. Chun-Yuan Chang & Jianming Wang & Yuhan Zhao & Juan Liu & Xue Yang & Xuetian Yue & Huaying Wang & Fan Zhou & Juan M. Inclan-Rico & John J. Ponessa & Ping Xie & Lanjing Zhang & Mark C. Siracusa & Zhaoh, 2021. "Tumor suppressor p53 regulates intestinal type 2 immunity," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Huiyuan Zhu & Man Li & Dexi Bi & Huiqiong Yang & Yaohui Gao & Feifei Song & Jiayi Zheng & Ruting Xie & Youhua Zhang & Hu Liu & Xuebing Yan & Cheng Kong & Yefei Zhu & Qian Xu & Qing Wei & Huanlong Qin, 2024. "Fusobacterium nucleatum promotes tumor progression in KRAS p.G12D-mutant colorectal cancer by binding to DHX15," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Ori Hassin & Nishanth Belugali Nataraj & Michal Shreberk-Shaked & Yael Aylon & Rona Yaeger & Giulia Fontemaggi & Saptaparna Mukherjee & Martino Maddalena & Adi Avioz & Ortal Iancu & Giuseppe Mallel & , 2022. "Different hotspot p53 mutants exert distinct phenotypes and predict outcome of colorectal cancer patients," Nature Communications, Nature, vol. 13(1), pages 1-15, 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:15:y:2024:i:1:d:10.1038_s41467-023-44390-w. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.