異なるヘルパーＴ細胞による腸管ＩｇＡの変化と腸内細菌叢への影響の検討

2014 Fiscal Year Annual Research Report

• Project/Area Number: 13F03216
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: ファガラサン シドニア 独立行政法人理化学研究所, 統合生命医科学研究センター, チームリーダー (00391970)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Lucia 独立行政法人理化学研究所, 統合生命医科学研究センター, 外国人特別研究員
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: IgA / Foxp3 / gut bacteria / Peyer's patches / germinal center

Outline of Annual Research Achievements

The aim of the project was to dissect the contribution of the adaptive immune system in establishing the symbiosis between host and bacteria in the gut.
We found that: 1) mice deficient for B cells, T cells or both, fail to support complex bacterial communities in the gut; 2) the reconstitution of T cell-deficient mice with CD4+ T cells expressing the transcription factor Foxp3 (Foxp3+ T cells) restores both the diversity and the phylogenetic structure of bacteria; 3) Foxp3+ T cells helped diversification particularly of the non-virulent Clostridia species, which were recently reported to induce Foxp3. This means that not only Clostridia induce Foxp3, but that the Foxp3+ T cells contribute to the persistence and diversification of Clostridia of the Firmicutes (the most diverse bacterial species in both mice and humans); 4) Foxp3+ T cells act outside and inside germinal centers, by preventing inflammation and by regulating selection of IgAs, respectively; 5) the coating of bacteria with selected IgAs was required to maintain the bacteria in the gut and to prevent the expansion of opportunistic species which could become pathogenic.
The research was published in Immunity, 2014.

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] The role of the adaptive immune system in regulation of gut microbiota (2014)
  • Author(s): Lucia M. Kato, Shimpei Kawamoto, Mikako Maruya, Sidonia Fagarasan
  • Journal Title: Immunological Reviews Volume: 260 Pages: 67-75
  • DOI: 10.1111/imr.12185
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Foxp3+ T Cells Regulate Immunoglobulin A Selection and Facilitate Diversification of Bacterial Species Responsible for Immune Homeostasis (2014)
  • Author(s): Shimpei Kawamoto, Mikako Maruya, Lucia M. Kato, Wataru Suda, Koji Atarashi, Yasuko Doi, Yumi Tsutsui, Hongyan Qin, Kenya Honda, Takaharu Okada, Masahira Hattori, and Sidonia Fagarasan
  • Journal Title: Immunity Volume: 41 Pages: 152-165
  • DOI: http://dx.doi.org/10.1016/j.immuni.2014.05.016
  • Peer Reviewed / Open Access / Acknowledgement Compliant