The influence of TCR specificity of T follicular helper cells on gut IgA production

• Project/Area Number: 25860375
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KAWAMOTO SHIMPEI 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, 研究員 (40612081)
• Research Collaborator: 丸谷 美香子 ; 加藤 ルシア
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 免疫グロブリンA / 腸内細菌叢 / Foxp3+T細胞 / 濾胞性ヘルパーT細胞 / 濾胞制御性T細胞 / IgA / パイエル板 / 腸内細菌

Outline of Final Research Achievements

Foxp3+ T cells play a critical role for the maintenance of immune tolerance. We show that in mice, Foxp3+ T cells contributed to diversification of gut microbiota, particularly of species belonging to Firmicutes, Clostridia. Diversified and selected immunoglobulin A (IgA)s, which are regulated by Foxp3+ T cells in germinal centers (GCs) of Peyer’s patches, contributed to maintenance of diversified and balanced microbiota, which in turn facilitated the expansion of Foxp3+ T cells, induction of GCs, and IgA responses in the gut through a symbiotic regulatory loop. Thus, the adaptive immune system, through cellular and molecular components that are required for immune tolerance and through the diversification as well as selection of antibody repertoire, mediates host-microbial symbiosis by controlling the richness and balance of bacterial communities required for homeostasis.

Research Products

• [Journal Article] The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. (2015)
  • Author(s): Vasanthakumar A, Moro K, Xin A, Liao Y, Gloury R, Kawamoto S, Fagarasan S, Mielke LA, Afshar-Sterle S, Masters SL, Nakae S, Saito H, Wentworth JM, Li P, Liao W, Leonard WJ, Smyth GK, Shi W, Nutt SL, Koyasu S, Kallies A
  • Journal Title: Nat Immunol. Volume: 16 Issue: 3 Pages: 276-285
  • DOI: 10.1038/ni.3085
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 濾胞性ヘルパーT細胞による免疫グロブリンAの選択機構 (2015)
  • Author(s): 河本新平、Fagarasan Sidonia
  • Journal Title: 炎症と免疫 Volume: 23 Pages: 27-31
• [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 Issue: 1 Pages: 152-165
  • DOI: 10.1016/j.immuni.2014.05.016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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 Issue: 1 Pages: 67-75
  • DOI: 10.1111/imr.12185
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gut TFH and IgA : key players for regulation of bacterial communities and immune homeostasis (2014)
  • Author(s): Kato LM, Kawamoto S, Maruya M, Fagarasan S
  • Journal Title: Immunology and Cell Biology Volume: 92 Issue: 1 Pages: 49-56
  • DOI: 10.1038/icb.2013.54
  • Peer Reviewed
• [Presentation] Foxp3+T細胞および免疫グロブリンAによる腸内細菌制御機構 (2015)
  • Author(s): 河本新平
  • Organizer: Midwinter Seminar 2015
  • Place of Presentation: ANAインターコンチネンタル万座ビーチホテル（沖縄）
  • Year and Date: 2015-02-25 – 2015-02-28
• [Presentation] Symbiotic regulatory loop between Foxp3+ T cells, IgA and gut microbiota (2014)
  • Author(s): 河本新平
  • Organizer: 2014年度 日本免疫学会総会
  • Place of Presentation: 京都国際会議場（京都）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Foxp3+T 細胞、IgA 及び腸内細菌叢の間に見られる相互制御ループの解明 (2014)
  • Author(s): 河本新平
  • Organizer: 第42 回日本臨床免疫学会総会
  • Place of Presentation: 京王プラザホテル（東京）
  • Year and Date: 2014-09-25
  • Invited
• [Presentation] 腸内細菌叢と腸管免疫 (2014)
  • Author(s): 河本新平
  • Organizer: 第56 回日本老年医学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2014-06-12 – 2014-06-14
  • Invited
• [Presentation] 抑制性受容体PD-1が腸管IgA産生および腸内細菌制御に与える影響の検討 (2013)
  • Author(s): 河本新平、丸谷美香子、加藤ルシア、Fagarasan Sidonia
  • Organizer: 第23回フローサイトメトリー学会
  • Place of Presentation: 日本医科大学（東京）
  • Invited
• [Presentation] The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. (2013)
  • Author(s): Kawamoto Shimpei, Tran Huy Thinh, Maruya Mikako, Suzuki Keiichiro, Doi Yasuko, Tsutsui Yumi, Kato Lucia Megumi, Fagarasan Sidonia
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: ミラノ（イタリア）
• [Remarks] Foxp3陽性T細胞，腸管の免疫グロブリンA，腸内フローラのあいだにみられる相互制御
  • URL: http://first.lifesciencedb.jp/archives/9110