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@ARTICLE{Kaiser:278067,
author = {Kaiser, Kim M and Raabe, Jan and ToVinh, Michael and Hack,
Gudrun and Ahmad, Sarah and Müller, Niko and Cassella,
Julia and Walravens, Sofia I and Alfaro, Paula and Arias
Garcia, Lauren and Kaczmarek, Dominik J and Marwitz, Tim and
Goeser, Felix and Nischalke, Hans Dieter and Lutz, Philipp
and Sommer, Nils and Vilz, Tim and Toma, Marieta and
Steiner, Susanne and Hommerding, Oliver and Oldenburg,
Johannes and Hölzel, Michael and Kadzik, Sebastian and
Maas, Alexander and Eckrich, Jonas and Zumfelde, Philipp and
Shakeri, Farhad and Nesic, Svetozar and Buness, Andreas and
De Caro, Emilia and Becker, Matthias and Beyer, Marc D and
Ulas, Thomas and Aschenbrenner, Anna C and Steinheuer, Lisa
M and Thurley, Kevin and Kroh, Sandy and Uecker, Ralf and
Hauser, Anja E and Gohr, Florian N and Schmidt, Florian I
and Wang, Danni and Held, Kathrin and Baranov, Olga and
Geldmacher, Christof and Strassburg, Christian P and
Hüneburg, Robert and Krämer, Benjamin and Nattermann,
Jacob},
title = {{IL}-17{A}-producing {NK}p44(-) group 3 innate lymphoid
cells accumulate in {F}amilial {A}denomatous {P}olyposis
duodenal tissue.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DZNE-2025-00558},
pages = {3873},
year = {2025},
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.},
keywords = {Interleukin-17: metabolism / Interleukin-17: genetics /
Interleukin-17: immunology / Humans / Dual Oxidases /
Adenomatous Polyposis Coli: immunology / Adenomatous
Polyposis Coli: genetics / Adenomatous Polyposis Coli:
pathology / Adenomatous Polyposis Coli: metabolism /
Lymphocytes: immunology / Lymphocytes: metabolism / Reactive
Oxygen Species: metabolism / Duodenum: pathology / Duodenum:
immunology / Duodenum: metabolism / Immunity, Innate / Male
/ Interleukin-23 Subunit p19: genetics / Interleukin-23
Subunit p19: metabolism / Female / Interleukin-1beta:
genetics / Interleukin-1beta: metabolism / Duodenal
Neoplasms: immunology / Duodenal Neoplasms: pathology /
Duodenal Neoplasms: genetics / Duodenal Neoplasms:
metabolism / Organoids: metabolism / NADPH Oxidases:
metabolism / NADPH Oxidases: genetics / Membrane Proteins:
genetics / Membrane Proteins: metabolism / DNA Damage /
Interleukin-17 (NLM Chemicals) / Dual Oxidases (NLM
Chemicals) / DUOX2 protein, human (NLM Chemicals) / Reactive
Oxygen Species (NLM Chemicals) / IL17A protein, human (NLM
Chemicals) / Interleukin-23 Subunit p19 (NLM Chemicals) /
IL23A protein, human (NLM Chemicals) / Interleukin-1beta
(NLM Chemicals) / NADPH Oxidases (NLM Chemicals) / IL1B
protein, human (NLM Chemicals) / Membrane Proteins (NLM
Chemicals)},
cin = {AG Schultze / PRECISE / AG Aschenbrenner / AG Beyer},
ddc = {500},
cid = {I:(DE-2719)1013038 / I:(DE-2719)1013031 /
I:(DE-2719)5000082 / I:(DE-2719)1013035},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354) / 352
- Disease Mechanisms (POF4-352) / 351 - Brain Function
(POF4-351)},
pid = {G:(DE-HGF)POF4-354 / G:(DE-HGF)POF4-352 /
G:(DE-HGF)POF4-351},
experiment = {EXP:(DE-2719)PRECISE-20190321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40280932},
pmc = {pmc:PMC12032359},
doi = {10.1038/s41467-025-58907-y},
url = {https://pub.dzne.de/record/278067},
}