TY  - JOUR
AU  - Kaiser, Kim M
AU  - Raabe, Jan
AU  - ToVinh, Michael
AU  - Hack, Gudrun
AU  - Ahmad, Sarah
AU  - Müller, Niko
AU  - Cassella, Julia
AU  - Walravens, Sofia I
AU  - Alfaro, Paula
AU  - Arias Garcia, Lauren
AU  - Kaczmarek, Dominik J
AU  - Marwitz, Tim
AU  - Goeser, Felix
AU  - Nischalke, Hans Dieter
AU  - Lutz, Philipp
AU  - Sommer, Nils
AU  - Vilz, Tim
AU  - Toma, Marieta
AU  - Steiner, Susanne
AU  - Hommerding, Oliver
AU  - Oldenburg, Johannes
AU  - Hölzel, Michael
AU  - Kadzik, Sebastian
AU  - Maas, Alexander
AU  - Eckrich, Jonas
AU  - Zumfelde, Philipp
AU  - Shakeri, Farhad
AU  - Nesic, Svetozar
AU  - Buness, Andreas
AU  - De Caro, Emilia
AU  - Becker, Matthias
AU  - Beyer, Marc D
AU  - Ulas, Thomas
AU  - Aschenbrenner, Anna C
AU  - Steinheuer, Lisa M
AU  - Thurley, Kevin
AU  - Kroh, Sandy
AU  - Uecker, Ralf
AU  - Hauser, Anja E
AU  - Gohr, Florian N
AU  - Schmidt, Florian I
AU  - Wang, Danni
AU  - Held, Kathrin
AU  - Baranov, Olga
AU  - Geldmacher, Christof
AU  - Strassburg, Christian P
AU  - Hüneburg, Robert
AU  - Krämer, Benjamin
AU  - Nattermann, Jacob
TI  - IL-17A-producing NKp44(-) group 3 innate lymphoid cells accumulate in Familial Adenomatous Polyposis duodenal tissue.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-00558
SP  - 3873
PY  - 2025
AB  - 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.
KW  - Interleukin-17: metabolism
KW  - Interleukin-17: genetics
KW  - Interleukin-17: immunology
KW  - Humans
KW  - Dual Oxidases
KW  - Adenomatous Polyposis Coli: immunology
KW  - Adenomatous Polyposis Coli: genetics
KW  - Adenomatous Polyposis Coli: pathology
KW  - Adenomatous Polyposis Coli: metabolism
KW  - Lymphocytes: immunology
KW  - Lymphocytes: metabolism
KW  - Reactive Oxygen Species: metabolism
KW  - Duodenum: pathology
KW  - Duodenum: immunology
KW  - Duodenum: metabolism
KW  - Immunity, Innate
KW  - Male
KW  - Interleukin-23 Subunit p19: genetics
KW  - Interleukin-23 Subunit p19: metabolism
KW  - Female
KW  - Interleukin-1beta: genetics
KW  - Interleukin-1beta: metabolism
KW  - Duodenal Neoplasms: immunology
KW  - Duodenal Neoplasms: pathology
KW  - Duodenal Neoplasms: genetics
KW  - Duodenal Neoplasms: metabolism
KW  - Organoids: metabolism
KW  - NADPH Oxidases: metabolism
KW  - NADPH Oxidases: genetics
KW  - Membrane Proteins: genetics
KW  - Membrane Proteins: metabolism
KW  - DNA Damage
KW  - Interleukin-17 (NLM Chemicals)
KW  - Dual Oxidases (NLM Chemicals)
KW  - DUOX2 protein, human (NLM Chemicals)
KW  - Reactive Oxygen Species (NLM Chemicals)
KW  - IL17A protein, human (NLM Chemicals)
KW  - Interleukin-23 Subunit p19 (NLM Chemicals)
KW  - IL23A protein, human (NLM Chemicals)
KW  - Interleukin-1beta (NLM Chemicals)
KW  - NADPH Oxidases (NLM Chemicals)
KW  - IL1B protein, human (NLM Chemicals)
KW  - Membrane Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40280932
C2  - pmc:PMC12032359
DO  - DOI:10.1038/s41467-025-58907-y
UR  - https://pub.dzne.de/record/278067
ER  -