Interleukin 33 Triggers Early Eosinophil-Dependent Events Leading to Metaplasia in a Chronic Model of Gastritis-Prone Mice.

Autor:	De Salvo C; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Pastorelli L; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio; Gastroenterology Unit, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, San Donato Milanese, Milan, Italy; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy., Petersen CP; Department of Surgery and the Epithelial Biology Center, Vanderbilt University, Nashville, Tennessee., Buttò LF; Division of Gastroenterology & Liver Disease, Department Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio., Buela KA; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Omenetti S; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Locovei SA; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio; Division of Gastroenterology & Liver Disease, Department Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio., Ray S; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Friedman HR; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Duijser J; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Xin W; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Osme A; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Cominelli F; Division of Gastroenterology & Liver Disease, Department Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio., Mahabeleshwar GH; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Mills JC; Gastroenterology Division, Department of Medicine, Washington University in St. Louis School of Medicine, St Louis, Missouri., Goldenring JR; Department of Surgery and the Epithelial Biology Center, Vanderbilt University, Nashville, Tennessee., Pizarro TT; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio. Electronic address: theresa.pizarro@case.edu.
Jazyk:	angličtina
Zdroj:	Gastroenterology [Gastroenterology] 2021 Jan; Vol. 160 (1), pp. 302-316.e7. Date of Electronic Publication: 2020 Oct 01.
DOI:	10.1053/j.gastro.2020.09.040
Abstrakt:	Background & Aims: Interleukin (IL)33/IL1F11 is an important mediator for the development of type 2 T-helper cell (Th2)-driven inflammatory disorders and has also been implicated in the pathogenesis of gastrointestinal (GI)-related cancers, including gastric carcinoma. We therefore sought to mechanistically determine IL33's potential role as a critical factor linking chronic inflammation and gastric carcinogenesis using gastritis-prone SAMP1/YitFc (SAMP) mice. Methods: SAMP and (parental control) AKR mice were assessed for baseline gastritis and progression to metaplasia. Expression/localization of IL33 and its receptor, ST2/IL1R4, were characterized in corpus tissues, and activation and neutralization studies were both performed targeting the IL33/ST2 axis. Dissection of immune pathways leading to metaplasia was evaluated, including eosinophil depletion studies using anti-IL5/anti-CCR3 treatment. Results: Progressive gastritis and, ultimately, intestinalized spasmolytic polypeptide-expressing metaplasia (SPEM) was detected in SAMP stomachs, which was absent in AKR but could be moderately induced with exogenous, recombinant IL33. Robust peripheral (bone marrow) expansion of eosinophils and local recruitment of both eosinophils and IL33-expressing M2 macrophages into corpus tissues were evident in SAMP. Interestingly, IL33 blockade did not affect bone marrow-derived expansion and local infiltration of eosinophils, but markedly decreased M2 macrophages and SPEM features, while eosinophil depletion caused a significant reduction in both local IL33-producing M2 macrophages and SPEM in SAMP. Conclusions: IL33 promotes metaplasia and the sequelae of eosinophil-dependent downstream infiltration of IL33-producing M2 macrophages leading to intestinalized SPEM in SAMP, suggesting that IL33 represents a critical link between chronic gastritis and intestinalizing metaplasia that may serve as a potential therapeutic target for preneoplastic conditions of the GI tract. (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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