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Interleukin-9 production by type 2 innate lymphoid cells induces Paneth cell metaplasia and small intestinal remodeling. Nat Commun 2023 Dec 02;14(1):7963

Date

12/03/2023

Pubmed ID

38042840

Pubmed Central ID

PMC10693577

DOI

10.1038/s41467-023-43248-5

Scopus ID

2-s2.0-85178369915 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

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.

Author List

Yuan C, Rayasam A, Moe A, Hayward M, Wells C, Szabo A, Mackenzie A, Salzman N, Drobyski WR

Authors

William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Alison Moe PhD Research Scientist II in the Medicine department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Data Science Institute department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Immunity, Innate
Interleukin-33
Interleukin-9
Intestine, Small
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphocytes
Metaplasia
Mice
Paneth Cells