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DOI10.1073/pnas.2017432118
The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells
Wang Y.; He K.; Sheng B.; Lei X.; Tao W.; Zhu X.; Wei Z.; Fu R.; Wang A.; Bai S.; Zhang Z.; Hong N.; Ye C.; Tian Y.; Wang J.; Li M.; Zhang K.; Li L.; Yang H.; Li H.-B.; Flavell R.A.; Zhu S.
发表日期2021
ISSN00278424
卷号118期号:4
英文摘要RNA helicases play roles in various essential biological processes such as RNA splicing and editing. Recent in vitro studies show that RNA helicases are involved in immune responses toward viruses, serving as viral RNA sensors or immune signaling adaptors. However, there is still a lack of in vivo data to support the tissue- or cell-specific function of RNA helicases owing to the lethality of mice with complete knockout of RNA helicases; further, there is a lack of evidence about the antibacterial role of helicases. Here, we investigated the in vivo role of Dhx15 in intestinal antibacterial responses by generating mice that were intestinal epithelial cell (IEC)-specific deficient for Dhx15 (Dhx15 f/f Villin1-cre, Dhx15ΔIEC). These mice are susceptible to infection with enteric bacteria Citrobacter rodentium (C. rod), owing to impaired α-defensin production by Paneth cells. Moreover, mice with Paneth cell-specific depletion of Dhx15 (Dhx15 f/f Defensinα6-cre, Dhx15ΔPaneth) are more susceptible to DSS (dextran sodium sulfate)-induced colitis, which phenocopy Dhx15ΔIEC mice, due to the dysbiosis of the intestinal microbiota. In humans, reduced protein levels of Dhx15 are found in ulcerative colitis (UC) patients. Taken together, our findings identify a key regulator of Wnt-induced α-defensins in Paneth cells and offer insights into its role in the antimicrobial response as well as intestinal inflammation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Alpha-defensins; DEAD-box helicase 15 (Dhx15); Inflammatory bowel diseases (IBD); Intestinal inflammation; Paneth cells
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180870
作者单位Department of Digestive Disease, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China; Hefei National Laboratory for Physical Sciences at Microscale, Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, United States; State Key Laboratory of Molecular Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Networks, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, Chin...
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GB/T 7714
Wang Y.,He K.,Sheng B.,et al. The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells[J],2021,118(4).
APA Wang Y..,He K..,Sheng B..,Lei X..,Tao W..,...&Zhu S..(2021).The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells.Proceedings of the National Academy of Sciences of the United States of America,118(4).
MLA Wang Y.,et al."The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).
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