IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50223-1.html
   My bibliography  Save this article

Ribonuclease 4 functions as an intestinal antimicrobial protein to maintain gut microbiota and metabolite homeostasis

Author

Listed:
  • Jun Sun

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Muxiong Chen

    (Zhejiang University School of Medicine)

  • Zhen Hu

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Ningqin Xu

    (Hangzhou Normal University)

  • Wenguang Wang

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Zejun Ping

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Jiayi Zhu

    (Zhejiang University School of Medicine)

  • Desen Sun

    (Medical School of Ningbo University)

  • Zhehao Zhu

    (Zhejiang University)

  • Hangyu Li

    (Zhejiang University)

  • Xiaolong Ge

    (Zhejiang University School of Medicine)

  • Liang Luo

    (Zhejiang University School of Medicine)

  • Wei Zhou

    (Zhejiang University School of Medicine)

  • Rongpan Bai

    (Zhejiang University School of Medicine)

  • Zhengping Xu

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Jinghao Sheng

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University
    Zhejiang University School of Medicine)

Abstract

Antimicrobial proteins contribute to host-microbiota interactions and are associated with inflammatory bowel disease (IBD), but our understanding on antimicrobial protein diversity and functions remains incomplete. Ribonuclease 4 (Rnase4) is a potential antimicrobial protein with no known function in the intestines. Here we find that RNASE4 is expressed in intestinal epithelial cells (IEC) including Paneth and goblet cells, and is detectable in human and mouse stool. Results from Rnase4-deficient mice and recombinant protein suggest that Rnase4 kills Parasutterella to modulate intestinal microbiome, thereby enhancing indoleamine-2,3-dioxygenase 1 (IDO1) expression and subsequently kynurenic and xanthurenic acid production in IECs to reduce colitis susceptibility. Furthermore, deceased RNASE4 levels are observed in the intestinal tissues and stool from patients with IBD, correlating with increased stool Parasutterella. Our results thus implicate Rnase4 as an intestinal antimicrobial protein regulating gut microbiota and metabolite homeostasis, and as a potential diagnostic biomarker and therapeutic target for IBD.

Suggested Citation

  • Jun Sun & Muxiong Chen & Zhen Hu & Ningqin Xu & Wenguang Wang & Zejun Ping & Jiayi Zhu & Desen Sun & Zhehao Zhu & Hangyu Li & Xiaolong Ge & Liang Luo & Wei Zhou & Rongpan Bai & Zhengping Xu & Jinghao , 2024. "Ribonuclease 4 functions as an intestinal antimicrobial protein to maintain gut microbiota and metabolite homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50223-1
    DOI: 10.1038/s41467-024-50223-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50223-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-50223-1?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:15:y:2024:i:1:d:10.1038_s41467-024-50223-1. 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.