Spatial immunological network at mucosal immune system

• Project/Area Number: 22689015
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: JUN Kunisawa 東京大学, 医科学研究所, 准教授 (80376615)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000); Fiscal Year 2011: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000); Fiscal Year 2010: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
• Keywords: 粘膜免疫 / イメージング / 感染症

Research Abstract

In this study, we performed an immunological studies using some imaging system for analyzing bacterial distribution and growth as well as host immune system at mucosal tissues. Using chemiluminescence-based microbial detection system, we can evaluate nasal vaccine effects against Streptococcus pneumoniae. As host immune system, we identified M cell-like cells in the epithelial cell layer of the nasal cavity as a new pathogen uptake pathway. In addition, macro-confocal laser microscopy allowed us to reveal the unique dendritic cell function in the formation of T cell areas in the Peyer's patches by regulating the retention rather than entering step of T cells in the Peyer's patches. Taken together, our imaging systems reveal the novel immunological functions and bacterial distribution and growth, which can be applied to the basic immunological analyses and the evaluation of mucosal vaccines.

Research Products

• [Journal Article] A pivotal role of vitamin B9 in the maintenance of regulatory T cells in vitro and in vivo (2012)
  • Author(s): J. Kunisawa, E. Hashimoto, I. Ishikawa,and H. Kiyono
  • Journal Title: PLoS One Volume: 7
• [Journal Article] Membrane-bound human SCF/KL promotes in vivo human hematopoietic engraftment and myeloid differentiation (2012)
  • Author(s): S. Takagi, Y. Saito, A. Hijikata, S.Tanaka, T. Watanabe, T. Hasegawa, S. Mochizuki, J. Kunisawa, H. Kiyono, H. Koseki, O. Ohara, T. Saito, S. Taniguchi, L. D. Shultz, F. Ishikawa
  • Journal Title: Blood Volume: 119 Pages: 2768-77
• [Journal Article] A pivotal role of vitamin B9 in the maintenance of regulatory T cells in vitro and in ViVO (2012)
  • Author(s): J. Kunisawa, et al
  • Journal Title: PLoS One Volume: 7 Issue: 2 Pages: e32094-e32094
  • DOI: 10.1371/journal.pone.0032094
  • Peer Reviewed
• [Journal Article] The airway antigen sampling system: respiratory M cells as an alternative gateway for inhaled antigens (2011)
  • Author(s): D. Y., Kim, A. Sato, S. Fukuyama, H.Sagara, T. Nagatake, I. G. Kong, K. Goda, T. Nochi, J. Kunisawa, S. Sato, Y. Yokota, C. H. Lee, and H. Kiyono
  • Journal Title: J Immunol Volume: 186 Pages: 4253-62
• [Journal Article] Peaceful mutualism in the gut: Revealing key commensal bacteria for the creation and maintenance of immunological homeostasis (2011)
  • Author(s): J. Kunisawa and H. Kiyono
  • Journal Title: Cell Host Microbe Volume: 9 Pages: 83-84
• [Journal Article] 粘膜表層における生体防御システムとしての粘膜免疫機能 (2011)
  • Author(s): 和氣太一、國澤純、清野宏
  • Journal Title: 表面 Volume: 49 Pages: 13-22
  • NAID: 40019241955
• [Journal Article] IgA産生における腸内免疫ネットワーク (2011)
  • Author(s): 國澤純
  • Journal Title: 実験医学増刊免疫記憶の制御と疾患治療 Volume: 29 Pages: 100-105
• [Journal Article] 腸内細菌のパイエル板組織内共生 (2011)
  • Author(s): 國澤純、後藤義幸、小幡高士、清野宏
  • Journal Title: 細胞工学 Volume: 30 Pages: 409-412
• [Journal Article] マクロ共焦点顕微鏡を用いた粘膜組織における細胞動態 (2011)
  • Author(s): 國澤純
  • Journal Title: Drug Delivery System Volume: 26 Pages: 419-421
• [Journal Article] 食物アレルギーの予防および治療的戦略の確立に向けた粘膜免疫研究の展開 (2011)
  • Author(s): 倉島洋介、網谷岳朗、國澤純、清野宏
  • Journal Title: アレルギー免疫 Volume: 18 Pages: 66-77
• [Journal Article] lgA産生における腸内免疫ネットワーク (2011)
  • Author(s): 國澤純
  • Journal Title: 実験医学増刊 免疫記憶の制御と疾患治療 Volume: 29 Pages: 100-105
• [Journal Article] R.Ooka, T.Sato, K.Harayama, S.Murakami, Y.Kawamoto (2011)
  • Author(s): J Kunisawa, H Kiyono
  • Journal Title: Cell Host Microbe Volume: 9 Pages: 83-84
  • Peer Reviewed
• [Journal Article] Peaceful mutualism in the gut : Revealing key commensal bacteria for the creation and maintenance of immunological homeostasis (2011)
  • Author(s): DY Kim, et al
  • Journal Title: J Immunol 186:4253-62,2011 Volume: 186 Pages: 4253-62
  • Peer Reviewed
• [Journal Article] Interleukin-1 family cytokines as mucosal vaccine adjuvants for induction of protective immunity against influenza virus (2010)
  • Author(s): H. Kayamuro, Y. Yoshioka, Y. Abe, S.Arita, K. Katayama, T. Nomura, T. Yoshikawa, R. Kubota-Koketsu, K. Ikuta, S. Okamoto, Y. Mori, J. Kunisawa, H. Kiyono, N. Itoh, K. Nagano, H. Kamada, Y. Tsutsumi, S.I. Tsunoda
  • Journal Title: J Virol Volume: 84 Pages: 12703-12
• [Journal Article] Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis (2010)
  • Author(s): T. Obata, Y. Goto, J. Kunisawa, S. Sato, M. Sakamoto, H. Setoyama, T. Matsuki,K. Nonaka, N. Shibata, M. Gohda, Y. Kagiyama, T. Nochi, Y. Yuki, Y. Fukuyama, A. Mukai, S. Shinzaki, K. Fujihashi, C. Sasakawa, H. Iijima, M. Goto, Y. Umesaki, Y. Benno, and H. Kiyono
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 7419-24
• [Journal Article] Aberrant interaction of gut immune system with environmental factors in the development of food allergy (2010)
  • Author(s): J. Kunisawa and H. Kiyono
  • Journal Title: Curr Aller Asthma Rep Volume: 10 Pages: 215-221
• [Journal Article] 腸管の生体防御や恒常性維持における脂質メディエーター:スフィンゴシン1リン酸の役割 (2010)
  • Author(s): 國澤純
  • Journal Title: 化学と生物 Volume: 48 Pages: 827-830
• [Journal Article] 粘膜免疫の新展開-生体最前線における腸内環境との調和と排除- (2010)
  • Author(s): 國澤純
  • Journal Title: 無菌生物 Volume: 40 Pages: 25-28
  • NAID: 10026666315
• [Journal Article] The airway antigen sampling system : respiratory M cells as an alternative gateway for inhaled antigens (2010)
  • Author(s): T.Obata, et al
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 7419-24
  • Peer Reviewed
• [Journal Article] Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis (2010)
  • Author(s): J Kunisawa, H Kiyono
  • Journal Title: Curr Aller Asthma Rep Volume: 10 Pages: 215-21
  • Peer Reviewed
• [Journal Article] Aberrant interaction of gut immune system with environmental factors in the development of food allergy (2010)
  • Author(s): H.Kayamuro, et al
  • Journal Title: J Virol Volume: 84 Pages: 12703-12
  • Peer Reviewed
• [Journal Article] 腸管の生体防御や恒常性維持における脂質メディェーター:スフィンゴシン1リン酸の役割 (2010)
  • Author(s): 國澤純
  • Journal Title: 化学と生物 Volume: 48 Pages: 827-830
• [Presentation] 冬虫夏関連化合物FTY720からの新展開-腸管における生体防御と恒常性維持における脂質とビタミンの役割- (2011)
  • Author(s): 國澤純
  • Organizer: 第32回和漢医薬学総合研究所特別セミナー
  • Place of Presentation: 富山(富山県民会館)
  • Year and Date: 2011-12-10
• [Presentation] 冬虫夏草関連化合物FTY720からの新展開-腸管における生体防御と恒常性維持における脂質とビタミンの役割- (2011)
  • Author(s): 國澤純
  • Organizer: 第32回和漢医薬学総合研究所特別セミナー
  • Place of Presentation: 富山(富山県民会館)(招待)
  • Year and Date: 2011-12-10
• [Presentation] 粘膜免疫からみたワクチン効果 (2011)
  • Author(s): 國澤純
  • Organizer: 第54回日本感染症学会中日本地方会学術集会
  • Place of Presentation: 奈良(奈良県新公会堂)
  • Year and Date: 2011-11-26
• [Presentation] 粘膜免疫からみたワクチン効果 (2011)
  • Author(s): 國澤純
  • Organizer: 第54回日本感染症学会中日本地方会学術集会
  • Place of Presentation: 奈良(奈良県新公会堂)(招待)
  • Year and Date: 2011-11-26
• [Presentation] Immunological crosstalk with commensal bacteria in the regulation of intestinal IgA responses (2011)
  • Author(s): 國澤純
  • Organizer: 消化管と短鎖脂肪酸シンポジウム
  • Place of Presentation: 東京(日本大学)
  • Year and Date: 2011-11-19
• [Presentation] Immunological crosstalk with commensal bacteria in the regulation of intestinal IgA responses (2011)
  • Author(s): 國澤純
  • Organizer: 消化管と短鎖脂肪酸シンポジウム
  • Place of Presentation: 東京(日本大学)(招待)
  • Year and Date: 2011-11-19
• [Presentation] 食餌性分子を介した腸管免疫の制御と免疫疾患との関連 (2011)
  • Author(s): 國澤純
  • Organizer: 第53回日本消化器病学会大会
  • Place of Presentation: 福岡(福岡国際会議所)
  • Year and Date: 2011-10-21
• [Presentation] 食餌性分子を介した腸管免疫の制御と免疫疾患との関連 (2011)
  • Author(s): 國澤純
  • Organizer: 第53回日本消化器病学会大会
  • Place of Presentation: 福岡(福岡国際会議所)(招待)
  • Year and Date: 2011-10-21
• [Presentation] Lipids and vitamins in the regulation of gut immunity (2011)
  • Author(s): Jun Kunisawa
  • Organizer: JAFI 2011
  • Place of Presentation: 東京(東京大学)
  • Year and Date: 2011-10-18
• [Presentation] Lipids and vitamins in the regulation of gut immunity (2011)
  • Author(s): Jun Kunisawa
  • Organizer: JAFI 2011
  • Place of Presentation: 東京(東京大学)(招待)
  • Year and Date: 2011-10-18
• [Presentation] Keeping the immunological balance in the gut-functional food and health, (2011)
  • Author(s): Jun Kunisawa and Hiroshi Kiyono,
  • Organizer: Asia-Pacific Week 2011 Food forum, Berlin
  • Place of Presentation: Germany
  • Year and Date: 2011-09-08
• [Presentation] Keeping the immunological balance in the gut-functional food and health (2011)
  • Author(s): Jun Kunisawa, Hiroshi Kiyono
  • Organizer: Asia-Pacific Week 2011 Food forum
  • Place of Presentation: Berlin, Germany(招待)
  • Year and Date: 2011-09-08
• [Presentation] A Critical Role of Dietary Vitamin B9 in the Survival of Intestinal Regulatory T Cells and Consequent IgA Responses (2011)
  • Author(s): Jun Kunisawa
  • Organizer: ICMI 2011
  • Place of Presentation: Martinsried, Germany
  • Year and Date: 2011-07-07
• [Presentation] 共生細菌による腸管免疫制御システム (2011)
  • Author(s): 國澤純
  • Organizer: 第20回内毒素・LPS研究会
  • Place of Presentation: 東京(順天堂大学)
  • Year and Date: 2011-06-25
• [Presentation] 共生細菌による腸管免疫制御システム (2011)
  • Author(s): 國澤純
  • Organizer: 第20回内毒素・LPS研究会
  • Place of Presentation: 東京(順天堂大学)(招待)
  • Year and Date: 2011-06-25
• [Presentation] 腸粘膜表層と腸管組織内における免疫共生システム (2011)
  • Author(s): 國澤純
  • Organizer: 第15回腸内細菌学会
  • Place of Presentation: 東京(東京大学)
  • Year and Date: 2011-06-16
• [Presentation] 腸粘膜表層と腸管組織内における免疫共生システム (2011)
  • Author(s): 國澤純
  • Organizer: 第15回腸内細菌学会
  • Place of Presentation: 東京(東京大学)(招待)
  • Year and Date: 2011-06-16
• [Presentation] Dietary Vitamin B9 is a Survival Factor of Intestinal Regulatory T Cells (2011)
  • Author(s): Jun Kunisawa, Eri Hashimoto, Izumi Ishikawa, Hiroshi Kiyono
  • Organizer: AAI 2011
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-05-15
• [Presentation] Dietary Vitamin B9 is a Survival Factor of Intestinal Regulatory T Cells (2011)
  • Author(s): Jun Kunisawa, Eri Hashimoto, Izumi Ishikawa, Hiroshi Kiyono
  • Organizer: AAI 2011
  • Place of Presentation: San Fransisco, USA
  • Year and Date: 2011-05-15
• [Presentation] The uniqueness of mucosa-associated lymphoid tissues for the development of mucosal vaccine (2011)
  • Author(s): Jun Kunisawa
  • Organizer: BIT Life Sciences' 3rd World Congress of Vaccine
  • Place of Presentation: Beijing, China
  • Year and Date: 2011-03-23
• [Presentation] The uniqueness of mucosa-associated lymphoid tissues for the development of mucosal vaccine (2011)
  • Author(s): Jun Kunisawa and Hiroshi Kiyono
  • Organizer: BIT Life Sciences' 3World Congress of Vaccine
  • Place of Presentation: Beijing,China
  • Year and Date: 2011-03-01
• [Presentation] 次世代感染症ワクチンとしての粘膜ワクチン (2011)
  • Author(s): 國澤純
  • Organizer: 第28回日本医学会総会
  • Place of Presentation: 東京
• [Presentation] The Unique pathway in the development and maintenance of mucosa-associated lymphoid tissues (2010)
  • Author(s): Jun Kunisawa, et al
  • Organizer: 2nd Workshop of Synthetic Immunology
  • Place of Presentation: 京都
  • Year and Date: 2010-12-17
• [Presentation] Immunological function of sphingosine 1-phosphate in the regulation of innate and acquired phases of intestinal IgA responses (2010)
  • Author(s): Jun Kunisawa
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] New trend for oral vaccine development : Control of vitamin B9-mediated regulatory T cell function to enhance the vaccine antigen-specific IgA antibody responses (2010)
  • Author(s): Jun Kunisawa, et al
  • Organizer: 4th Vaccine and ISV Annual Global Congress
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2010-10-04
• [Presentation] Amelioration of gut inflammation by the regulation of P2X7 purinoceptor-mediated mast cell activation (2010)
  • Author(s): Yosuke Kurashima, et al
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-26
• [Presentation] Development of functional human myeloid subsets in NOD/SCID/IL2rγKO mice (2010)
  • Author(s): Satoshi Tanaka, et al
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-26
• [Presentation] MyD88-mediated high-IgA-secreting plasma cells for the effective mucosal immunity (2010)
  • Author(s): Jun Kunisawa, et al
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-25
• [Presentation] Double negative dendritic cells retain naive T cells in the interfollicular region of Peyer's patches (2010)
  • Author(s): Naoko Shibata, et al
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-24
• [Presentation] Vitamin B6-Mediated Sphingosine 1-Phosphate Metabolism in the Immunological Homeostasis in the Gut (2010)
  • Author(s): Jun Kunisawa, Hiroshi Kiyono
  • Organizer: ISSFAL2010
  • Place of Presentation: Maastricht, Netherland
  • Year and Date: 2010-06-01
• [Presentation] The Unique pathway in the development and maintenance of mucosa-associated lymphoid tissues (2010)
  • Author(s): Jun Kunisawa, Takahiro Nagatake, Takashi Obata, Naoko Shibata, and Hiroshi Kiyono
  • Organizer: 2ndWorkshop of Synthetic Immunology
  • Place of Presentation: 京都
• [Presentation] Immunological function of sphingosine 1-phosphate in the regulation of innate and acquired phases of intestinalIgA responses (2010)
  • Author(s): Jun Kunisawa
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
• [Presentation] Regulation of IgA antibody responses by immunological crosstalk with intestinal environmental factors (2010)
  • Author(s): Jun Kunisawa
  • Organizer: 第5回千葉大学G-COEシンポジウム
  • Place of Presentation: 東京
• [Presentation] 次世代ワクチンとしての粘膜免疫とDDS (2010)
  • Author(s): 國澤純
  • Organizer: 第26回日本DDS学会
  • Place of Presentation: 大阪
• [Presentation] MyD88 mediates intestinal IgA production in the maintenance of appropriate composition of commensal bacteria (2010)
  • Author(s): Jun Kunisawa and Hiroshi Kiyono
  • Organizer: The Second International Conference on Modern Mucosal Vaccine, Adjuvants & Micrbicides
  • Place of Presentation: Dublin, Ireland
• [Presentation] 粘膜組織における免疫学的普遍性と特殊性 (2010)
  • Author(s): 國澤純
  • Organizer: 第10回鎌倉カンファレンス
  • Place of Presentation: 横浜
• [Book] ドラッグデリバリーシステムの新展開II (2012)
  • Author(s): 國澤純
  • Total Pages: 279
  • Publisher: シーエムシー出版
• [Book] 腸内共生系のバイオサイエンス-腸内細菌と免疫の関係- (2011)
  • Author(s): 國澤純
  • Total Pages: 292
  • Publisher: 財団法人日本ビフィズス菌センター
• [Book] Methods in Microbiology (2011)
  • Author(s): J.Kunisawa, et al
  • Publisher: Academic Press
• [Book] 腸内共生系のバイオサイエンス-腸内細菌と免疫の関係- (2011)
  • Author(s): 國澤純
  • Publisher: 丸善
• [Book] 臨床粘膜免疫学 (2010)
  • Author(s): 國澤純
  • Publisher: 株式会社シナジー
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/EnMen/index_j.html