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A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury

Author

Listed:
  • Marco Calafiore

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Ya-Yuan Fu

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Paola Vinci

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Viktor Arnhold

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Winston Y. Chang

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Suze A. Jansen

    (University Medical Center Utrecht, Utrecht University
    Princess Máxima Center for Pediatric Oncology)

  • Anastasiya Egorova

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Shuichiro Takashima

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    National Hospital Organization Kyushu Medical Center, Fukuoka)

  • Jason Kuttiyara

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Takahiro Ito

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Jonathan Serody

    (University of North Carolina)

  • Susumu Nakae

    (Hiroshima University, Higashi-Hiroshima City)

  • Heth Turnquist

    (University of Pittsburgh School of Medicine)

  • Johan van Es

    (Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW))

  • Hans Clevers

    (Princess Máxima Center for Pediatric Oncology
    Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW)
    Roche Pharma Research and Early Development)

  • Caroline A. Lindemans

    (University Medical Center Utrecht, Utrecht University
    Princess Máxima Center for Pediatric Oncology)

  • Bruce R. Blazar

    (University of Minnesota)

  • Alan M. Hanash

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College
    Weill Cornell Medical College)

Abstract

Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as an intestinal injury biomarker, regulates intrinsic epithelial regeneration by inducing production of epidermal growth factor (EGF). Three-dimensional imaging and lineage-specific RiboTag induction within the stem cell compartment indicated that ISCs expressed IL-33 in response to radiation injury. Neighboring Paneth cells responded to IL-33 by augmenting production of EGF, which promoted ISC recovery and epithelial regeneration. These findings reveal an unknown pathway of niche regulation and crypt regeneration whereby the niche responds dynamically upon injury and the stem cells orchestrate regeneration by regulating their niche. This regenerative circuit also highlights the breadth of IL-33 activity beyond immunomodulation and the therapeutic potential of EGF administration for treatment of intestinal injury.

Suggested Citation

  • Marco Calafiore & Ya-Yuan Fu & Paola Vinci & Viktor Arnhold & Winston Y. Chang & Suze A. Jansen & Anastasiya Egorova & Shuichiro Takashima & Jason Kuttiyara & Takahiro Ito & Jonathan Serody & Susumu N, 2023. "A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40993-5
    DOI: 10.1038/s41467-023-40993-5
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    References listed on IDEAS

    as
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