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Paneth cell alpha-defensin misfolding correlates with dysbiosis and ileitis in Crohn's disease model mice

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Title: Paneth cell alpha-defensin misfolding correlates with dysbiosis and ileitis in Crohn's disease model mice
Authors: Shimizu, Yu Browse this author
Nakamura, Kiminori Browse this author
Yoshii, Aki Browse this author
Yokoi, Yuki Browse this author
Kikuchi, Mani Browse this author
Shinozaki, Ryuga Browse this author
Nakamura, Shunta Browse this author
Ohira, Shuya Browse this author
Sugimoto, Rina Browse this author
Ayabe, Tokiyoshi Browse this author →KAKEN DB
Issue Date: Jun-2020
Publisher: Life Science Alliance
Journal Title: Life Science Alliance
Volume: 3
Issue: 6
Start Page: e201900592
Publisher DOI: 10.26508/lsa.201900592
Abstract: Crohn's disease (CD) is an intractable inflammatory bowel disease, and dysbiosis, disruption of the intestinal microbiota, is associated with CD pathophysiology. ER stress, disruption of ER homeostasis in Paneth cells of the small intestine, and alpha-defensin misfolding have been reported in CD patients. Because alpha-defensins regulate the composition of the intestinal microbiota, their misfolding may cause dysbiosis. However, whether ER stress, alpha-defensin misfolding, and dysbiosis contribute to the pathophysiology of CD remains unknown. Here, we show that abnormal Paneth cells with markers of ER stress appear in SAMP1/YitFc, a mouse model of CD, along with disease progression. Those mice secrete reduced-form alpha-defensins that lack disulfide bonds into the intestinal lumen, a condition not found in normal mice, and reduced-form alpha-defensins correlate with dysbiosis during disease progression. Moreover, administration of reduced-form alpha-defensins to wild-type mice induces the dysbiosis. These data provide novel insights into CD pathogenesis induced by dysbiosis resulting from Paneth cell alpha-defensin misfolding and they suggest further that Paneth cells may be potential therapeutic targets.
Type: article
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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