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R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease

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Title: R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease
Authors: Hayase, Eiko Browse this author
Hashimoto, Daigo Browse this author →KAKEN DB
Nakamura, Kiminori Browse this author →KAKEN DB
Noizat, Clara Browse this author
Ogasawara, Reiki Browse this author
Takahashi, Shuichiro Browse this author
Ohigashi, Hiroyuki Browse this author
Yokoi, Yuki Browse this author
Sugimoto, Rina Browse this author
Matsuoka, Satomi Browse this author
Ara, Takahide Browse this author
Yokoyama, Emi Browse this author
Yamakawa, Tomohiro Browse this author
Ebata, Ko Browse this author
Kondo, Takeshi Browse this author →KAKEN DB
Hiramine, Rina Browse this author
Aizawa, Tomoyasu Browse this author →KAKEN DB
Ogura, Yoshitoshi Browse this author
Hayashi, Tetsuya Browse this author
Mori, Hiroshi Browse this author
Kurokawa, Ken Browse this author
Tomizuka, Kazuma Browse this author
Ayabe, Tokiyoshi Browse this author →KAKEN DB
Teshima, Takanori Browse this author →KAKEN DB
Issue Date: 4-Dec-2017
Publisher: Rockefeller University Press
Journal Title: Journal of experimental medicine
Volume: 214
Issue: 12
Start Page: 3507
End Page: 3518
Publisher DOI: 10.1084/jem.20170418
Abstract: The intestinal microbial ecosystem is actively regulated by Paneth cell-derived antimicrobial peptides such as α-defensins. Various disorders, including graft-versus-host disease (GVHD), disrupt Paneth cell functions, resulting in unfavorably altered intestinal microbiota (dysbiosis), which further accelerates the underlying diseases. Current strategies to restore the gut ecosystem are bacteriotherapy such as fecal microbiota transplantation and probiotics, and no physiological approach has been developed so far. In this study, we demonstrate a novel approach to restore gut microbial ecology by Wnt agonist R-Spondin1 (R-Spo1) or recombinant α-defensin in mice. R-Spo1 stimulates intestinal stem cells to differentiate to Paneth cells and enhances luminal secretion of α-defensins. Administration of R-Spo1 or recombinant α-defensin prevents GVHD-mediated dysbiosis, thus representing a novel and physiological approach at modifying the gut ecosystem to restore intestinal homeostasis and host-microbiota cross talk toward therapeutic benefits.
Rights: ©Eiko Hayase, et al., 2017. Originally published in Journal of Experimental Medicine. https://doi.org/10.1084/jem.20170418
https://creativecommons.org/licenses/by-nc-sa/4.0/
Type: article
URI: http://hdl.handle.net/2115/68336
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 橋本 大吾

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