Interferon-γ is a direct driver of crypt hyperplasia in celiac disease.

IF 13.6 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Jorunn Stamnaes, Daniel Stray, M Fleur du Pré, Louise F Risnes, Alisa E Dewan, Jakeer Shaik, Maria Stensland, Knut Ea Lundin, Ludvig M Sollid
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引用次数: 0

Abstract

Crypt hyperplasia is a key feature of celiac disease and several other small intestinal inflammatory conditions. Analysis of the gut epithelial crypt zone by mass spectrometry-based tissue proteomics revealed a strong interferon-γ (IFN-γ) signal in active celiac disease. This signal, hallmarked by increased expression of MHC molecules, was paralleled by diminished expression of proteins associated with fatty acid metabolism. Crypt hyperplasia and the same proteomic changes were observed in wild type mice administered IFN-γ. In mice with conditional knockout of the IFN-γ receptor in gut epithelial cells these signature morphological and proteomic changes were not induced on IFN-γ administration. IFN-γ is thus a driver of crypt hyperplasia in celiac disease by acting directly on crypt epithelial cells. The results are relevant to other enteropathies with involvement of IFN-γ.

干扰素-γ是乳糜泻隐窝增生的直接驱动因子。
隐窝增生是乳糜泻和其他小肠炎症的主要特征。基于质谱的组织蛋白质组学分析显示,在活动性乳糜泻中存在强干扰素-γ (IFN-γ)信号。该信号以MHC分子表达增加为特征,与脂肪酸代谢相关的蛋白质表达减少相对应。野生型小鼠给予IFN-γ后,观察到隐窝增生和相同的蛋白质组学变化。在有条件敲除肠道上皮细胞中IFN-γ受体的小鼠中,这些特征的形态学和蛋白质组学变化未被IFN-γ诱导。因此,IFN-γ通过直接作用于隐窝上皮细胞,是乳糜泻隐窝增生的驱动因素。该结果与IFN-γ参与的其他肠病有关。
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来源期刊
Journal of Clinical Investigation
Journal of Clinical Investigation 医学-医学:研究与实验
CiteScore
24.50
自引率
1.30%
发文量
1034
审稿时长
2 months
期刊介绍: The Journal of Clinical Investigation, established in 1924 by the ASCI, is a prestigious publication that focuses on breakthroughs in basic and clinical biomedical science, with the goal of advancing the field of medicine. With an impressive Impact Factor of 15.9 in 2022, it is recognized as one of the leading journals in the "Medicine, Research & Experimental" category of the Web of Science. The journal attracts a diverse readership from various medical disciplines and sectors. It publishes a wide range of research articles encompassing all biomedical specialties, including Autoimmunity, Gastroenterology, Immunology, Metabolism, Nephrology, Neuroscience, Oncology, Pulmonology, Vascular Biology, and many others. The Editorial Board consists of esteemed academic editors who possess extensive expertise in their respective fields. They are actively involved in research, ensuring the journal's high standards of publication and scientific rigor.
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