Home > Publications Database > IL-17A-producing NKp44(-) group 3 innate lymphoid cells accumulate in Familial Adenomatous Polyposis duodenal tissue. > print

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024 7 _ |a 10.1038/s41467-025-58907-y
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037 _ _ |a DZNE-2025-00558
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Kaiser, Kim M
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245 _ _ |a IL-17A-producing NKp44(-) group 3 innate lymphoid cells accumulate in Familial Adenomatous Polyposis duodenal tissue.
260 _ _ |a [London]
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|b Springer Nature
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520 _ _ |a 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.
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650 _ 7 |a Interleukin-17
|2 NLM Chemicals
650 _ 7 |a Dual Oxidases
|0 EC 1.11.1.-
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650 _ 7 |a DUOX2 protein, human
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650 _ 7 |a Reactive Oxygen Species
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650 _ 7 |a IL17A protein, human
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650 _ 7 |a Interleukin-23 Subunit p19
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650 _ 7 |a IL23A protein, human
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650 _ 7 |a Interleukin-1beta
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650 _ 7 |a NADPH Oxidases
|0 EC 1.6.3.-
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650 _ 7 |a IL1B protein, human
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650 _ 7 |a Membrane Proteins
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650 _ 2 |a Interleukin-17: metabolism
|2 MeSH
650 _ 2 |a Interleukin-17: genetics
|2 MeSH
650 _ 2 |a Interleukin-17: immunology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Dual Oxidases
|2 MeSH
650 _ 2 |a Adenomatous Polyposis Coli: immunology
|2 MeSH
650 _ 2 |a Adenomatous Polyposis Coli: genetics
|2 MeSH
650 _ 2 |a Adenomatous Polyposis Coli: pathology
|2 MeSH
650 _ 2 |a Adenomatous Polyposis Coli: metabolism
|2 MeSH
650 _ 2 |a Lymphocytes: immunology
|2 MeSH
650 _ 2 |a Lymphocytes: metabolism
|2 MeSH
650 _ 2 |a Reactive Oxygen Species: metabolism
|2 MeSH
650 _ 2 |a Duodenum: pathology
|2 MeSH
650 _ 2 |a Duodenum: immunology
|2 MeSH
650 _ 2 |a Duodenum: metabolism
|2 MeSH
650 _ 2 |a Immunity, Innate
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Interleukin-23 Subunit p19: genetics
|2 MeSH
650 _ 2 |a Interleukin-23 Subunit p19: metabolism
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Interleukin-1beta: genetics
|2 MeSH
650 _ 2 |a Interleukin-1beta: metabolism
|2 MeSH
650 _ 2 |a Duodenal Neoplasms: immunology
|2 MeSH
650 _ 2 |a Duodenal Neoplasms: pathology
|2 MeSH
650 _ 2 |a Duodenal Neoplasms: genetics
|2 MeSH
650 _ 2 |a Duodenal Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Organoids: metabolism
|2 MeSH
650 _ 2 |a NADPH Oxidases: metabolism
|2 MeSH
650 _ 2 |a NADPH Oxidases: genetics
|2 MeSH
650 _ 2 |a Membrane Proteins: genetics
|2 MeSH
650 _ 2 |a Membrane Proteins: metabolism
|2 MeSH
650 _ 2 |a DNA Damage
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773 _ _ |a 10.1038/s41467-025-58907-y
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