Article

High-affinity monoclonal IgA regulates gut microbiota and prevents colitis in mice

  • Nature Microbiology 1, Article number: 16103 (2016)
  • doi:10.1038/nmicrobiol.2016.103
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Abstract

Immunoglobulin A (IgA) is the main antibody isotype secreted into the intestinal lumen. IgA plays a critical role in the defence against pathogens and in the maintenance of intestinal homeostasis. However, how secreted IgA regulates gut microbiota is not completely understood. In this study, we isolated monoclonal IgA antibodies from the small intestine of healthy mouse. As a candidate for an efficient gut microbiota modulator, we selected a W27 IgA, which binds to multiple bacteria, but not beneficial ones such as Lactobacillus casei. W27 could suppress the cell growth of Escherichia coli but not L. casei in vitro, indicating an ability to improve the intestinal environment. Indeed W27 oral treatment could modulate gut microbiota composition and have a therapeutic effect on both lymphoproliferative disease and colitis models in mice. Thus, W27 IgA oral treatment is a potential remedy for inflammatory bowel disease, acting through restoration of host–microbial symbiosis.

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Acknowledgements

The authors thank T. Honjo for providing AIDG23S and AID−/− mice, Dr H. Niki for providing E. coli strains ME9062 and JW2535, S. Nomura and M. Ohta for technical help, and T. Nakano, K. Asoh and V. Shivarov for critical reading. This work was supported by grants from the Japan Science and Technology Agency, JSPS KAKENHI 15H04732, Yakult Bio-Science Foundation, Naito Memorial Foundation, Senshin Medical Research Foundation and Astellas Foundation for Research on Metabolic Disorders (to R.S.) and also by AMED-CREST, AMED and RIKEN Pioneering Project ‘Biology of Symbiosis’ (to H.O.).

Author information

Author notes

    • Shinsaku Okai
    • , Fumihito Usui
    •  & Reiko Shinkura

    Present address: Applied Immunology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan

    • Shinsaku Okai
    •  & Fumihito Usui

    These authors contributed equally to this work.

Affiliations

  1. Department of Immunology, Nagahama Institute of Bioscience and Technology, Nagahama, Shiga 526-0829, Japan

    • Shinsaku Okai
    • , Fumihito Usui
    • , Shuhei Yokota
    • , Yusaku Hori-i
    •  & Reiko Shinkura
  2. Department of Protein Function Analysis, Nagahama Institute of Bioscience and Technology, Nagahama, Shiga 526-0829, Japan

    • Makoto Hasegawa
  3. Department of Epigenetics, Nagahama Institute of Bioscience and Technology, Nagahama, Shiga 526-0829, Japan

    • Toshinobu Nakamura
  4. Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto 606-8501, Japan

    • Manabu Kurosawa
  5. Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan

    • Seiji Okada
  6. Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Tokyo 152-8550, Japan

    • Kazuya Yamamoto
    • , Eri Nishiyama
    • , Hiroshi Mori
    •  & Takuji Yamada
  7. Earth-Life Science Institute, Tokyo Institute of Technology, Tokyo 152-8550, Japan

    • Ken Kurokawa
  8. Yakult Central Institute, Tokyo 186-8650, Japan

    • Satoshi Matsumoto
    • , Masanobu Nanno
    • , Tomoaki Naito
    •  & Yohei Watanabe
  9. RIKEN Center for Integrative Medical Sciences (IMS), Kanagawa 230-0045, Japan

    • Tamotsu Kato
    • , Eiji Miyauchi
    •  & Hiroshi Ohno
  10. Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

    • Hiroshi Ohno
  11. Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan

    • Hiroshi Ohno
  12. PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan

    • Reiko Shinkura

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Contributions

S.Okai, F.U. and R.S. designed and performed experiments, analysed data and wrote the paper. S.Okai, S.Y., Y.H., T.N. and M.K. performed pathological analyses. S.M., M.N., T.N. and Y.W. provided live anaerobic bacteria and performed bacterial qPCR analysis. M.H. performed mass spectrometry. S.Okai, R.S., S.M., E.M. and H.O. were involved in induced colitis experiments. E.M. and H.O. performed W27 binding bacterial sorting and related bioinformatics analyses. T.K., H.O., K.Y., E.N., H.M., T.Y. and K.K. performed microbiome bioinformatics analyses for antibody-treated mice. S.Okada provided essential materials. S.Okai, F.U., R.S., S.M., H.O., K.K., H.M., E.M. and T.K. were involved in data discussions.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Reiko Shinkura.

Supplementary information

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    Supplementary information

    Supplementary Tables 1–7, Supplementary Figures 1–6.