Interleukin-9 production by type 2 innate lymphoid cells induces Paneth cell metaplasia and small intestinal remodeling.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 Dec 2023
02 Dec 2023
Historique:
received:
17
10
2022
accepted:
03
11
2023
medline:
4
12
2023
pubmed:
3
12
2023
entrez:
2
12
2023
Statut:
epublish
Résumé
Paneth cell metaplasia (PCM) typically arises in pre-existing gastrointestinal (GI) diseases; however, the mechanistic pathway that induces metaplasia and whether PCM is initiated exclusively by disorders intrinsic to the GI tract is not well known. Here, we describe the development of PCM in a murine model of chronic myelogenous leukemia (CML) that is driven by an inducible bcr-abl oncogene. Mechanistically, CML induces a proinflammatory state within the GI tract that results in the production of epithelial-derived IL-33. The binding of IL-33 to the decoy receptor ST2 leads to IL-9 production by type 2 innate lymphoid cells (ILC2) which is directly responsible for the induction of PCM in the colon and tissue remodeling in the small intestines, characterized by goblet and tuft cell hyperplasia along with expansion of mucosal mast cells. Thus, we demonstrate that an extra-intestinal disease can trigger an ILC2/IL-9 immune circuit, which induces PCM and regulates epithelial cell fate decisions in the GI tract.
Identifiants
pubmed: 38042840
doi: 10.1038/s41467-023-43248-5
pii: 10.1038/s41467-023-43248-5
pmc: PMC10693577
doi:
Substances chimiques
Interleukin-9
0
Interleukin-33
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7963Informations de copyright
© 2023. The Author(s).
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