Mucosa-associated lymphoid tissue organogenesis by unique inducer cell subsets.

• Project/Area Number: 15K19142
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition
• Principal Investigator: Takahiro Nagatake 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 ワクチンマテリアルプロジェクト, 研究員 (80608737)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 粘膜関連リンパ組織形成 / リンパ組織誘導細胞 / パイエル板 / NALT / TALT / iBALT / 粘膜関連リンパ組織

Outline of Final Research Achievements

Mucosa-associated lymphoid tissues develop in various mucosal surfaces and play an important role in host defense. In this study, we found that respiratory lymphoid tissues develop using unique developmental programs that is different from intestinal and lacrimal lymphoid tissue programs. Further, we found that antibody response and allergic symptoms was normally induced in the absence of nasopharynx-associated lymphoid tissue, suggesting the presence of lymphoid tissue-independent immune systems in the upper respiratory tract. These findings indicate that respiratory immune system show uniqueness in tissue development and immune function which is a target of the development of effective nasal vaccine.

Research Products

• [Int'l Joint Research] トロント大学(カナダ)
• [Int'l Joint Research] Amgen(米国)
• [Journal Article] Fine Particles Induce Alveolar Macrophage Death and Interleukin-1α Release to Promote Inducible Bronchus-Associated Lymphoid Tissue Formation. (2016)
  • Author(s): Kuroda E, Ozasa K, Temizoz B, Ohata K, Koo CX, Kanuma T, Kusakabe T, Kobari S, Horie M, Morimoto Y, Nakajima S, Kabashima K, Ziegler SF, Iwakura Y, Ise W, Kurosaki T, Nagatake T, Kunisawa J, Takemura N, Uematsu S, Hayashi M, Aoshi T, Kobiyama K, Coban C, Ishii KJ.
  • Journal Title: Immunity. Volume: 45(6) Issue: 6 Pages: 1299-1310
  • DOI: 10.1016/j.immuni.2016.11.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mode of bioenergetic metabolism during B cell differentiation in the intestine determines the distinct requirement for vitamin B1 (2015)
  • Author(s): J. Kunisawa, Y. Sugiura, T. Wake, T. Nagatake, H. Suzuki, R. Nagasawa, S. Shikata, K. Honda, E. Hashimoto, Y. Suzuki, M. Setou, M. Suematsu, H. Kiyono
  • Journal Title: Cell Rep Volume: 13 Issue: 1 Pages: 122-131
  • DOI: 10.1016/j.celrep.2015.08.063
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut (2015)
  • Author(s): J. Kunisawa, M. Arita, T. Hayasaka, T. Harada, R. Iwamoto, R. Nagasawa, S. Shikata, T. Nagatake, H. Suzuki, E. Hashimoto, Y. Kurashima, Y. Suzuki, H. Arai, M. Setou, and H. Kiyono
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 9750-9750
  • DOI: 10.1038/srep09750
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Central role of core binding factor β2 in mucosa-associated lymphoid tissue organogenesis in mouse (2015)
  • Author(s): T. Nagatake, S. Fukuyama, S. Sato, H. Okura, M. Tachibana, I. Taniuchi, K. Ito, M. Shimojou, N. Matsumoto, H, Suzuki, J. Kunisawa, and H. Kiyono
  • Journal Title: PLoS ONE Volume: 10 Issue: 5 Pages: e0127460-e0127460
  • DOI: 10.1371/journal.pone.0127460
  • NAID: 120006987038
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] SIK3 deficiency exacerbates LPS-induced endotoxin shock accompanied by increased levels of proinflammatory molecules in mice. (2015)
  • Author(s): Sanosaka M, Fujimoto M, Ohkawara T, Nagatake T, Itoh Y, Kagawa M, Kumagai A, Fuchino H, Kunisawa J, Naka T, Takemori H
  • Journal Title: Immunology Volume: 144 Issue: 2 Pages: 268-278
  • DOI: 10.1111/imm.12445
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 17,18-EpETEは好中球の遊走を抑制することで接触性皮膚炎を軽減する. (2017)
  • Author(s): 長竹貴広、菊田順一、本田哲也、Prabha Tiwari、柳澤篤、石井優、椛島健治、國澤純.
  • Organizer: 第4回先進イメージング医学研究会・学術集会
  • Place of Presentation: 兵庫
  • Year and Date: 2017-02-20
• [Presentation] Organogenesis of inducible bronchus-associated lymphoid tissue has essential role in the induction of antigen-specific immune response by Ag85B-hPIV2-based anti-tuberculosis vaccine in mice. (2017)
  • Author(s): Nagatake T, Suzuki H, Nasu A, Hirata S, Wada Y, Matsumoto N, Shimojou M, Morimoto S, Hosomi K, Ogami K, Tsujimura Y, Kawano M, Nosaka T, Yasutomi Y, Kunisawa J.
  • Organizer: 第10回次世代アジュバント研究会
  • Place of Presentation: 大阪
  • Year and Date: 2017-01-23
• [Presentation] 17,18-epoxy-eicosatetraenoic acid ameliorated contact hypersensitivity by inhibiting neutrophil infiltration into the skin. (2016)
  • Author(s): Nagatake T, Honda T, Suzuki H, Arita M. Kiyono H, Kabashima K, Kunisawa J.
  • Organizer: 第45回日本免疫学会
  • Place of Presentation: 沖縄
  • Year and Date: 2016-12-05
  • Int'l Joint Research
• [Presentation] ロイコトリエンB4受容体BLT1はB細胞増殖を促進することで経口ワクチンに対する抗原特異的IgA抗体産生を促進する. (2016)
  • Author(s): 長竹貴広、平田宗一郎、古賀友紹、佐々木文之、鈴木英彦、細見晃司、横溝岳彦、國澤純.
  • Organizer: 第20回日本ワクチン学会
  • Place of Presentation: 東京
  • Year and Date: 2016-10-22
• [Presentation] Contact hypersensitivity is ameliorated by 17,18-epoxy-eicosatetraenoic acid, a metabolite from eicosapentaenoic acid, in the skin. (2016)
  • Author(s): Nagatake T, Shiogama Y, Honda T, Isobe Y, Arita M, Matsumoto N, Shimojou M, Tiwari P, Suzuki H, Yasutomi Y, Kiyono H, Kabashima K, Kunisawa J.
  • Organizer: International Congress of Immunology
  • Place of Presentation: メルボルン
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Contact hypersensitivity is ameliorated by 17,18-epoxy-eicosatetraenoic acid, a metabolite from eicosapentaenoic acid, in the skin (2016)
  • Author(s): Takahiro Nagatake, Yumiko Shiogama, Tetsuya Honda, Yosuke Isobe, Makoto Arita, Naomi Matsumoto, Michiko Shimojou, Prabha Tiwari, Hidehiko Suzuki, Yasuhiro Yasutomi, Hiroshi Kiyono, Kenji Kabashima, Jun Kunisawa
  • Organizer: 国際免疫学会
  • Place of Presentation: メルボルン
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Inducible bronchus-associated lymphoid tissue plays an important role in the induction of antigen-specific immune response by Ag85B-hPIV2-based anti-tuberculosis vaccine in mice. (2016)
  • Author(s): Nagatake T, Wada Y, Matsumoto N, Shimojou M, Hirata S, Nasu A, Suzuki H, Hosomi K, Ogami K, Tsujimura Y, Kawano M, Nosaka T, Yasutomi Y, Kunisawa J.
  • Organizer: The 103rd Annual Meeting of The American Association of Immunologists
  • Place of Presentation: シアトル
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] Inducible bronchus-associated lymphoid tissue plays an important role in the induction of antigen-specific immune response by Ag85B-hPIV2-based anti-tuberculosis vaccine in mice (2016)
  • Author(s): Takahiro Nagatake, Yasuko Wada, Naomi Matsumoto, Michiko Shimojou, Soichiro Hirata, Ayaka Nasu, Hidehiko Suzuki, Koji Hosomi, Kentaro Ogami, Yusuke Tsujimura, Mitsuo Kawano, Tetsuya Nosaka, Yasuhiro Yasutomi, Kunisawa
  • Organizer: アメリカ免疫学会
  • Place of Presentation: シアトル
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] Essential role of inducible bronchus-associated lymphoid tissue genesis for the induction of antigen-specific immune response by Ag85B-hPIV2-based anti-tuberculosis vaccine in mice (2016)
  • Author(s): Takahiro Nagatake, Yasuko Wada, Naomi Matsumoto, Michiko Shimojou, Soichiro Hirata, Ayaka Nasu, Hidehiko Suzuki, Koji Hosomi, Kentaro Ogami, Yusuke Tsujimura, Mitsuo Kawano, Tetsuya Nosaka, Yasuhiro Yasutomi, Jun Kunisawa
  • Organizer: 第9回 次世代アジュバント研究会
  • Place of Presentation: 大阪
  • Year and Date: 2016-01-19
  • Int'l Joint Research
• [Presentation] Prevention of gut and skin allergic inflammation by 17,18-epoxy-eicosatetraenoic acid, an endogenously generated lipid metabolite from linseed oil (2015)
  • Author(s): Takahiro Nagatake, Makoto Arita, Tetsuya Honda, Hidehiko Suzuki, Hiroshi Kiyono, Kenji Kabashima, Jun Kunisawa
  • Organizer: 第44回 日本免疫学会
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
  • Int'l Joint Research
• [Presentation] 接触性皮膚炎モデルにおける17,18-EpETEの有効性評価 (2015)
  • Author(s): 長竹貴広、有田誠、本田哲也、磯部洋輔、松本直実、下條倫子、四方紫織、鈴木英彦、清野宏、椛島健治、國澤純
  • Organizer: 第57回 日本脂質生化学会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-28
• [Book] Lymphoid tissues associated with gastrointestinal (GI) mucosa.「Lymph Node Metastasis in Gastrointestinal Cancer」 (2017)
  • Author(s): Nagatake T, Kunisawa J, Kiyono H.
  • Publisher: Springer
• [Book] 食物アレルギーの発症における食用油クオリティの影響「化学と生物」 (2017)
  • Author(s): 長竹貴広、國澤純.
  • Publisher: 日本農芸化学会会誌
• [Book] 粘膜関連リンパ組織のユニーク性と臨床応用「リンパ学」 (2016)
  • Author(s): 中橋理佳、長竹貴広、清野宏.
  • Publisher: 日本リンパ学会機関誌
• [Book] 実験医学増刊号 脂質疾患学 (2015)
  • Author(s): 長竹貴広、國澤純
  • Total Pages: 6
  • Publisher: 羊土社
• [Book] 医学のあゆみ 粘膜免疫Update (2015)
  • Author(s): 長竹貴広、國澤純
  • Total Pages: 6
  • Publisher: 医歯薬出版