R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease
| Autor: | Hiroshi Mori, Hiroyuki Ohigashi, Ken Kurokawa, Satomi Matsuoka, Ko Ebata, Shuichiro Takahashi, Rina Hiramine, Tomohiro Yamakawa, Emi Yokoyama, Yoshitoshi Ogura, Tokiyoshi Ayabe, Rina Sugimoto, Takahide Ara, Tetsuya Hayashi, Kiminori Nakamura, Tomoyasu Aizawa, Reiki Ogasawara, Yuki Yokoi, Takanori Teshima, Eiko Hayase, Daigo Hashimoto, Kazuma Tomizuka, Takeshi Kondo, Clara Noizat |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Paneth Cells alpha-Defensins Cellular differentiation Immunology Antimicrobial peptides Administration Oral Graft vs Host Disease Biology digestive system 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Immunology and Allergy Secretion Research Articles Bacteria Stem Cells Brief Definitive Report Wnt signaling pathway Cell Differentiation medicine.disease Recombinant Proteins Cell biology Intestines Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Cytoprotection 030220 oncology & carcinogenesis Paneth cell Dysbiosis Female Stem cell Thrombospondins Bacteriotherapy Stem Cell Transplantation |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Hayase et al. show that R-Spondin1 stimulates intestinal stem cells to differentiate to Paneth cells and enhances luminal secretion of α-defensins. Administration of R-Spondin1 or recombinant α-defensin prevents dysbiosis mediated by graft-versus-host disease, representing a novel approach to restore intestinal ecosystems and homeostasis. 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. |
| Databáze: | OpenAIRE |
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