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)
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