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- W2903374927 abstract "Abstract Chronic inflammation of the gastric mucosa, often caused by autoimmune gastritis and/or infection with Helicobacter pylori , can lead to atrophy of acid‐secreting parietal cells with metaplasia of remaining cells. The histological pattern marks a critical step in the progression from chronic gastritis to gastric cancer, yet underlying mechanism(s) of inflammation‐induced cell death of gastric epithelial cells are poorly understood. We investigated direct effects of a type 1 cytokine associated with autoimmunity and infection, interferon‐γ (IFN‐γ), on gastric epithelial cells. IFN‐γ was applied to three‐dimensional organoid cultures of gastric epithelial cells derived from gastric corpus gland (gastroids) of control and IFN‐γ receptor‐deficient mice. Gastroids were also treated with supernatants from activated immune cells isolated from a mouse model of autoimmune‐mediated atrophic gastritis (TxA23) with and without IFN‐γ expression. Finally, histopathological analysis of atrophy and metaplasia severity was performed in TxA23 mice and compared to TxA23 × Ifng −/− mice. Gastric epithelial cells in gastroid cultures expressed IFN‐γ receptor in the basolateral membrane, and gastroids died when treated with IFN‐γ in an IFN‐γ receptor‐dependent manner. Supernatants from immune cells containing high levels of IFN‐γ were highly toxic to gastroids, and toxicity was tempered when IFN‐γ was either neutralized using a monoclonal antibody or when supernatants from Ifng −/− mouse immune cells were used. Finally, TxA23 × Ifng −/− mice showed near‐complete abrogation of pre‐cancerous histopathological atrophy and metaplasia versus IFN‐γ‐sufficient controls. We identify IFN‐γ as a critical promoter of parietal cell atrophy with metaplasia during the progression of gastritis to gastric atrophy and metaplasia. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd." @default.
- W2903374927 created "2018-12-11" @default.
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- W2903374927 date "2019-01-24" @default.
- W2903374927 modified "2023-09-30" @default.
- W2903374927 title "Interferon-γ directly induces gastric epithelial cell death and is required for progression to metaplasia" @default.
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- W2903374927 doi "https://doi.org/10.1002/path.5214" @default.
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