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Citations to this article

Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn’s disease
Michele M. Kosiewicz, … , Kosuke Kozaiwa, Fabio Cominelli
Michele M. Kosiewicz, … , Kosuke Kozaiwa, Fabio Cominelli
Published March 15, 2001
Citation Information: J Clin Invest. 2001;107(6):695-702. https://doi.org/10.1172/JCI10956.
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Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn’s disease

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Abstract

We describe here the immunologic characterization of a new mouse strain, SAMP1/Yit, which spontaneously develops a chronic intestinal inflammation localized to the terminal ileum. The resulting ileitis bears a remarkable resemblance to human Crohn’s disease. This strain of mice develops discontinuous, transmural inflammatory lesions in the terminal ileum with 100% penetrance by 30 weeks of age. The intestinal inflammation is characterized by massive infiltration of activated CD4+ and CD8α+TCRαβ+ T cells into the lamina propria and is accompanied by a dramatic decrease in the intraepithelial lymphocyte CD8α+TCRγδ+/CD8α+TCRαβ+ ratio. The results of adoptive transfer experiments strongly suggest that CD4+ T cells that produce a Th1-like profile of cytokines, e.g., IFN-γ and TNF, mediate the intestinal inflammation found in SAMP1/Yit mice. In addition, pretreatment of adoptive transfer recipients with a neutralizing anti-TNF antibody prevents the development of intestinal inflammation, suggesting that TNF plays an important role in the pathogenesis of intestinal inflammation in this model. To our knowledge, these data provide the first direct evidence that Th1-producing T cells mediate intestinal inflammation in a spontaneous animal model of human Crohn’s disease.

Authors

Michele M. Kosiewicz, Cynthia C. Nast, Anasuya Krishnan, Jesus Rivera-Nieves, Christopher A. Moskaluk, Satoshi Matsumoto, Kosuke Kozaiwa, Fabio Cominelli

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Year: 2025 2024 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 Total
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