Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells (original) (raw)

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DDBJ/GenBank/EMBL

Gene Expression Omnibus

Data deposits

The microarray and ChIP-seq analysis data have been deposited at the Gene Expression Omnibus (GEO) under accession number GSE49655. The microbiome analysis data have been deposited at the DDBJ database (http://getentry.ddbj.nig.ac.jp/) under accession number DRA001105.

Change history

• 12 February 2014

An Erratum to this paper has been published: https://doi.org/10.1038/nature13041

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Acknowledgements

We would like to thank P. Carninci, Y. Shinkai and M. Yoshida for discussion; Y. Chiba and S. Yamada for technical support; H. Sugahara for technical advice; and P. D. Burrows for critical reading and editing of the manuscript. This work was supported in part by grants from Japanese Ministry of Education, Culture, Sports, Science and Technology (24117524 to S.F.; 21022049 to K.Ha.; 20113003 to H.O.), The Japan Society for the Promotion of Science (24890293 to Y.F.; 252667 to Y.O.; 24380072 and 24658129 to S.F.; 22689017 to K.Ha.; 21390155 to H.O.), The Japan Science and Technology Agency (K.Ha., K.A. and K.Ho.), RIKEN President’s Special Research Grant (H.O.), RIKEN RCAI Young Chief Investigator program (K.Ha.), the Institute for Fermentation, Osaka (S.F.), the Mishima Kaiun Memorial Foundation (S.F.), The Takeda Science Foundation (S.F. and H.O.), The Mitsubishi Foundation (H.O.), and The Uehara Memorial Foundation (S.F. and K.Ha.).

Author information

Author notes

1. Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda and Koji Hase: These authors contributed equally to this work.

Authors and Affiliations

1. RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa 230-0045, Japan ,
   Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda, Takaho A. Endo, Gaku Nakato, Daisuke Takahashi, Chikako Uetake, Keiko Kato, Tamotsu Kato, Masumi Takahashi, Eiji Miyauchi, Koji Atarashi, Satoshi Onawa, Shohei Hori, Osamu Ohara, Haruhiko Koseki, Kenya Honda, Koji Hase & Hiroshi Ohno
2. The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan ,
   Yukihiro Furusawa, Yuuki Obata, Yumiko Fujimura & Koji Hase
3. Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan ,
   Yuuki Obata, Haruhiko Koseki & Hiroshi Ohno
4. Institute for Advanced Biosciences, Keio University, Yamagata 997-0052, Japan ,
   Shinji Fukuda, Yumiko Nakanishi, Noriko N. Fukuda, Shinnosuke Murakami & Masaru Tomita
5. Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan ,
   Keiko Kato, Haruhiko Koseki, Jun Kikuchi & Hiroshi Ohno
6. Faculty of Agriculture, Shizuoka University, Shizuoka 422-8529, Japan ,
   Shingo Hino & Tatsuya Morita
7. PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan ,
   Koji Atarashi & Koji Hase
8. Preventative Health National Research Flagship, CSIRO Food and Nutritional Sciences, South Australia 5000, Australia ,
   Trevor Lockett, Julie M. Clarke & David L. Topping
9. RIKEN Center for Sustainable Resource Science, Kanagawa 230-0045, Japan ,
   Jun Kikuchi
10. CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan ,
    Kenya Honda

Authors

1. Yukihiro Furusawa
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2. Yuuki Obata
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3. Shinji Fukuda
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4. Takaho A. Endo
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5. Gaku Nakato
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6. Daisuke Takahashi
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7. Yumiko Nakanishi
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8. Chikako Uetake
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9. Keiko Kato
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10. Tamotsu Kato
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11. Masumi Takahashi
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12. Noriko N. Fukuda
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13. Shinnosuke Murakami
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14. Eiji Miyauchi
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15. Shingo Hino
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16. Koji Atarashi
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17. Satoshi Onawa
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18. Yumiko Fujimura
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19. Trevor Lockett
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20. Julie M. Clarke
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21. David L. Topping
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22. Masaru Tomita
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23. Shohei Hori
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24. Osamu Ohara
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25. Tatsuya Morita
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26. Haruhiko Koseki
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27. Jun Kikuchi
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28. Kenya Honda
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29. Koji Hase
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30. Hiroshi Ohno
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Contributions

S.F., K.Ha., D.L.T., T.M., K.Ho. and H.O. conceived the study; K.Ha. and S.F. designed the experiments and wrote the manuscript with Y.Fur., Y.O. and H.O.; Y. Fur. and Y.O conducted a large part of experiments together with S.F., G.N., D.T., C.U., K.K., T.K., M.Ta., E.M. and K.Ha; S.F, S.O. and K.Ha. prepared germ-free, CRB-associated and gnotobiotic mice. K.A. and K.Ho. were involved in data discussion. S.F., Y.N., C.U. and J.K. performed metabolome analysis. S.F., T.K., S.M. and M.To. performed microbiome analysis. T.A.E. performed bioinformatic analyses. S.Hi. and T.M. performed HPLC analysis. S.F. and N.N.F. performed GC–MS analysis. Y.Fuj. performed histological analysis. T.L., J.M.C., D.L.T. and S.Ho. provided essential materials and contributed to the design of experiments. Y.Fur. and H.K. contributed to the ChIP assay. H.O. directed the study and took primary responsibility for editing the manuscript.

Corresponding authors

Correspondence toShinji Fukuda, Koji Hase or Hiroshi Ohno.

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The authors declare no competing financial interests.

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Furusawa, Y., Obata, Y., Fukuda, S. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.Nature 504, 446–450 (2013). https://doi.org/10.1038/nature12721

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• Received: 18 June 2013
• Accepted: 27 September 2013
• Published: 13 November 2013
• Issue Date: 19 December 2013
• DOI: https://doi.org/10.1038/nature12721