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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
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    References listed on IDEAS

    as
    1. Ken Cadwell & John Y. Liu & Sarah L. Brown & Hiroyuki Miyoshi & Joy Loh & Jochen K. Lennerz & Chieko Kishi & Wumesh Kc & Javier A. Carrero & Steven Hunt & Christian D. Stone & Elizabeth M. Brunt & Ram, 2008. "A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells," Nature, Nature, vol. 456(7219), pages 259-263, November.
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