TY - JOUR
T1 - R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease
AU - Hayase, Eiko
AU - Hashimoto, Daigo
AU - Nakamura, Kiminori
AU - Noizat, Clara
AU - Ogasawara, Reiki
AU - Takahashi, Shuichiro
AU - Ohigashi, Hiroyuki
AU - Yokoi, Yuki
AU - Sugimoto, Rina
AU - Matsuoka, Satomi
AU - Ara, Takahide
AU - Yokoyama, Emi
AU - Yamakawa, Tomohiro
AU - Ebata, Ko
AU - Kondo, Takeshi
AU - Hiramine, Rina
AU - Aizawa, Tomoyasu
AU - Ogura, Yoshitoshi
AU - Hayashi, Tetsuya
AU - Mori, Hiroshi
AU - Kurokawa, Ken
AU - Tomizuka, Kazuma
AU - Ayabe, Tokiyoshi
AU - Teshima, Takanori
N1 - Funding Information:
This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology/Japan Society for the Promotion of Science KAKENHI (25293217 and 221S0002 to T. Teshima, 26461438 to D. Hashimoto, 26462831 to K. Nakamura, and 26440072 to T. Aizawa), Health and Labor Science Research grants from the Ministry of Health, Labour and Welfare (to T. Teshima), the Promotion and Standardization of the Tenure-Track System (to D. Hashimoto), the Astellas Foundation for Research on Metabolic Disorders (to D. Hashimoto), the Takeda Science Foundation (to D. Hashimoto), SENSHIN Medical Research Foundation (to D. Hashimoto), Global Station for Soft Matter, a project of the Global Institution for Collaborative Research and Education at Hokkaido University (to T. Aizawa), and the Center of Innovation Program from the Japan Science and Technology Agency (to T. Teshima, K. Nakamura, and T. Ayabe.). The authors declare competing financial interests: T. Teshima is a recipient of a research grant from Kyowa Hakko Kirin.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20170418
DO - 10.1084/jem.20170418
M3 - Article
C2 - 29066578
AN - SCOPUS:85036571700
VL - 214
SP - 3507
EP - 3518
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 12
ER -