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IL-17A-producing NKp44(−) group 3 innate lymphoid cells accumulate in Familial Adenomatous Polyposis duodenal tissue

Author

Listed:
  • Kim M. Kaiser

    (University Hospital Bonn)

  • Jan Raabe

    (University Hospital Bonn)

  • Michael ToVinh

    (University Hospital Bonn)

  • Gudrun Hack

    (University Hospital Bonn)

  • Sarah Ahmad

    (University Hospital Bonn)

  • Niko Müller

    (University Hospital Bonn)

  • Julia Cassella

    (University Hospital Bonn)

  • Sofia I. Walravens

    (University Hospital Bonn)

  • Paula Alfaro

    (University Hospital Bonn)

  • Lauren Arias Garcia

    (University Hospital Bonn)

  • Dominik J. Kaczmarek

    (University Hospital Bonn
    University Hospital Bonn)

  • Tim Marwitz

    (University Hospital Bonn
    University Hospital Bonn)

  • Felix Goeser

    (University Hospital Bonn)

  • Hans Dieter Nischalke

    (University Hospital Bonn)

  • Philipp Lutz

    (University Hospital Bonn)

  • Nils Sommer

    (University Hospital Bonn)

  • Tim Vilz

    (University Hospital Bonn
    University Hospital Bonn)

  • Marieta Toma

    (University Hospital Bonn)

  • Susanne Steiner

    (University Hospital Bonn)

  • Oliver Hommerding

    (University Hospital Bonn
    University Hospital Bonn)

  • Johannes Oldenburg

    (University Hospital Bonn)

  • Michael Hölzel

    (University Hospital Bonn)

  • Sebastian Kadzik

    (University Hospital Bonn)

  • Alexander Maas

    (University Hospital Bonn)

  • Jonas Eckrich

    (University Medical Center Mainz)

  • Philipp Zumfelde

    (Gastroenterology)

  • Farhad Shakeri

    (University of Bonn)

  • Svetozar Nesic

    (University of Bonn)

  • Andreas Buness

    (University of Bonn)

  • Emilia Caro

    (Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
    University of Bonn)

  • Matthias Becker

    (Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE))

  • Marc D. Beyer

    (Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
    Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
    and West German Genome Center)

  • Thomas Ulas

    (Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
    University of Bonn
    and West German Genome Center)

  • Anna C. Aschenbrenner

    (Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE))

  • Lisa M. Steinheuer

    (University Hospital Bonn)

  • Kevin Thurley

    (University Hospital Bonn
    Leibniz Association)

  • Sandy Kroh

    (Leibniz Association
    Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Ralf Uecker

    (Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    a Leibniz Institute)

  • Anja E. Hauser

    (Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    a Leibniz Institute)

  • Florian N. Gohr

    (University of Bonn)

  • Florian I. Schmidt

    (University of Bonn)

  • Danni Wang

    (LMU Munich)

  • Kathrin Held

    (LMU Munich
    German Center for Infection Research (DZIF))

  • Olga Baranov

    (LMU Munich)

  • Christof Geldmacher

    (LMU Munich
    German Center for Infection Research (DZIF))

  • Christian P. Strassburg

    (University Hospital Bonn
    University Hospital Bonn)

  • Robert Hüneburg

    (University Hospital Bonn
    University Hospital Bonn)

  • Benjamin Krämer

    (University Hospital Bonn)

  • Jacob Nattermann

    (University Hospital Bonn
    University Hospital Bonn
    German Center for Infection Research (DZIF))

Abstract

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Even among carriers of the same genetic variant, duodenal phenotypes vary, indicating that additional factors, such as the local immune system, play a role. We observe an increase in duodenal IL-17A(+)NKp44(−) innate lymphoid type 3 cell (ILC3) in FAP, localized near the epithelium and enriched in adenomas and carcinomas. Elevated IL1B, IL23A, and DLL4 transcript levels correlate with IL-17A(+)NKp44(−)ILC3 accumulation, and in vitro studies with duodenal organoids confirmed this relationship. Bulk RNA sequencing reveals upregulated Reactive oxygen species (ROS)-inducing enzymes DUOX2 and DUOXA2 in FAP adenomas. IL-17A-stimulated FAP organoids show increased DUOX2/DUOXA2 expression, Duox2 protein, and ROS production, leading to DNA damage, suggesting a mechanism by which these immune cells promote tumorigenesis. These findings suggest IL-17A(+)NKp44(–)ILC3s may contribute to a local environment that makes the epithelium more submissive for oncogenic transformation in FAP.

Suggested Citation

  • Kim M. Kaiser & Jan Raabe & Michael ToVinh & Gudrun Hack & Sarah Ahmad & Niko Müller & Julia Cassella & Sofia I. Walravens & Paula Alfaro & Lauren Arias Garcia & Dominik J. Kaczmarek & Tim Marwitz & F, 2025. "IL-17A-producing NKp44(−) group 3 innate lymphoid cells accumulate in Familial Adenomatous Polyposis duodenal tissue," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58907-y
    DOI: 10.1038/s41467-025-58907-y
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    References listed on IDEAS

    as
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