サイトカインを基盤とするアレルギー病態の生体内イメージング

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24249058
• Research Institution: Tokyo University of Science
• Principal Investigator: 久保 允人 東京理科大学, 生命医科学研究所, 教授 (40277281)
• Co-Investigator(Kenkyū-buntansha): 原田 陽介 東京理科大学, 生命医科学研究所, 助教 (20328579) ; 宮内 浩典 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 (50619856)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 免疫学 / アレルギー / T細胞

Outline of Annual Research Achievements

近年、従来のアレルギー炎症はTh2から産生されるIL-4により制御されると言ったTh2を中心にアレルギー性炎症病態が考えられてきたが、これらTh2サイトカインはTh2細胞のみならず、自然免疫系を構成するNKT細胞、肥満細胞、好塩基球やNatural Helper細胞等からも産生される。本研究では、生体内レベルで起こるアレルギー反応を対象にこれら疑問に答えていくことを目的に、サイトカインレポーターマウスなどを使うことで、生体内動態のイメージングを行い、アレルギー炎症に対する次世代治療戦略の基盤形成を目指す。本年度の研究計画では、TH2細胞によって誘導されるIgE抗体産生制御機構を明らかにして行くことで、IgE抗体の産生機構を明らかにする。

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] Notch signaling enhances FceRI-mediated cytokine production by mast cells through direct and indirect mechanisms (2015)
  • Author(s): Nakano, N., Nishiyama, C., Yagita, H., Hara, M., Motomura, Y., Kubo, M., Okumura, K., and Ogawa, H
  • Journal Title: J. Immunol Volume: 194(9) Pages: 4535-44
  • DOI: 10.4049/jimmunol.1301850
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Zinc-binding metallothioneins are key modulators of IL-4 production by basophils (2015)
  • Author(s): Ugajin, T., Nishida, K., Yamasaki, S., Suzuki, J., Mita, M., Kubo, M., Yokozeki, H., Hirano, T
  • Journal Title: Molecular Immunology Volume: 66(2) Pages: 180-188
  • DOI: 10.1016/j.molimm.2015.03.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] NFIL3 orchestrates the emergence of common helper innate lymphoid cell precursors (2015)
  • Author(s): Wei Xu, Rita G. Domingues, Diogo Fonseca-Pereira, Manuela Ferreira, Hélder Ribeiro, Silvia Lopez-Lastra, Yasutaka Motomura, Lara Moreira-Santos, Franck Bihl4, Véronique Braud, Barbara Kee, Hugh Brady, Mark C.Coles, Christian Vosshenrich, Kubo, M., James P. Di Santo and Henrique Veiga-Fernandes
  • Journal Title: Cell Report Volume: 10(12) Pages: 2043-54
  • DOI: 10.1016/j.celrep.2015.02.057
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Perivascular leukocyte cluster are essential for efficient activation of effector T cell in the skin (2014)
  • Author(s): Natsuaki, Y., Egawa, G., Nakamizo, S., Hanakawa, S., Ono, S., Okada, T., Kusuba, N., Otsuka, A., Kitoh, A., Honda, T., Nakajima, S., Tsuchiya, S., Sugimoto, Y., Ishii, J. K., Tsutsui, H., Yagita, H., Iwakura, Y., Kubo, M., Hashimoto, T., Fuentes, J., Guttman-Yassky, E., Miyachi, Y., and Kabashima, K
  • Journal Title: Nature Immunology Volume: 15(11) Pages: 1064-9
  • DOI: 10.1038/ni.2992
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Basophils Promote Innate Lymphoid Cell Responses in Inflamed Skin (2014)
  • Author(s): Brian S. Kim, Mark C. Siracusa, Kelvin Wang, Steven A. Saenz, Kubo, M., and David Artis
  • Journal Title: J. Immunol Volume: 193(7) Pages: 3717-25
  • DOI: 10.4049/jimmunol.1401307
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cell (2014)
  • Author(s): Wataru Ise, Takeshi Inoue, James B McLachlan, Kohei Kometani, Kubo, M., Takaharu Okada and Tomohiro Kurosaki
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. Volume: 111(32) Pages: 11792-7
  • DOI: 10.1073/pnas.1404671111
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sphingosine-1-phosphate receptor 2 is critical for follicular helper T cell retention in germinal centers (2014)
  • Author(s): Moriyama, S., Takahashi, N., Green, J.A., Kubo, M., Cyster J.G. and Okada, T
  • Journal Title: J.Exp.Med Volume: 211(7) Pages: 1297-305
  • DOI: 10.1084/jem.20131666
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Basophil-derived interleukin-4 controls the function of natural helper cells, a member of ILC2s, in lung inflammation (2014)
  • Author(s): Motomura, Y., Morita, H., Moro, K., Nakae, S., Artis, D., Koyasu,S., Kubo, M
  • Journal Title: Immunity Volume: 40(5) Pages: 758-71
  • DOI: 10.1016/j.immuni.2014.04.013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The enzyme Cyp26b1 mediates inhibition of mast cell activation by fibroblasts to maintain skin-barrier homeostasis (2014)
  • Author(s): Kurashima, Y., Amiya, T., Fujisawa, K., Shibata, N., Suzuki, Y., Kogure, Y., Hashimoto, E., Otsuka, A., Kabashima, K., Sato, S., Kubo, M., Yokota, Y., Akira, S., Miyake, K., Kunisawa, J., and Kiyono, H.
  • Journal Title: Immunity Volume: 40(4) Pages: 530-41
  • DOI: 10.1016/j.immuni.2014.01.014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Basophils regulate the recruitment of eosinophils in a murine model of irritant contact dermatitis (2014)
  • Author(s): Nakashima, C., Otsuka, A., Kitoh, A., Honda,T., Egawa,G., Nakajima,S., Nakamizo,S., Arita, M., Kubo, M., Miyachi,Y., and Kabashima, K
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 134(1) Pages: 100-7
  • DOI: 10.1016/j.jaci.2014.02.026
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis (2014)
  • Author(s): Noti, M., Kim, B.S., Siracusa, M.C., Rak, G.D., Kubo, M., Moghaddam, A.E., Sattentau, Q.A., Comeau, M.R., Spergel, J.M., and Artis, D
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 133(5) Pages: 1390-9
  • DOI: 10.1016/j.jaci.2014.01.021
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] IL-17A as an inducer for Th2 immune responses in murine atopic dermatitis models (2014)
  • Author(s): Nakajima, S., Kitoh, A., Egawa, G., Natsuaki, Y., Nakamizo, S., Moniaga, C.A., Otsuka, A., Honda, T., Hanakawa, S., Amano, W., Iwakura, Y., Nakae, S., Kubo, M., Miyachi,Y., and Kabashima, K
  • Journal Title: Journal of Investigative Dermatology Volume: 134(8) Pages: 2122-30
  • DOI: 10.1038/jid.2014.51
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] E4BP4 (NFIL-3) affects the expression level of IFN-γ in Lin-CD127+NKp46- Innate lymphoid cells (2014)
  • Author(s): OMI Ai, MOTOMURA Yasutaka, KUBO Masato
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都府（国立京都国際会館）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Notch signaling promotes Tfh memory cell generation by facilitating migration into survival niche (2014)
  • Author(s): HARADA Yohsuke, TOKOYODA Koji, HANAZAWA Asami, KUBO Masato
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都府（国立京都国際会館）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] TH2 derived IgE antibody response in germinal center-dependent and independent ways (2014)
  • Author(s): HARADA Yasuyo, TAKEMORI Toshitada, KUBO Masato
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都府（国立京都国際会館）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Influenza A virus (IAV) vaccination effectively induces germinal center (2014)
  • Author(s): MIYAUCHI Kosuke, SUGIMOTO-ISHIGE Akiko, TAKAHASHI Yoshimasa, HASEGAWA Hideki, TAKEMORI Toshitada, KUBO Masato
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都府（国立京都国際会館）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Role of T follicular helper cells in influenza virus protection (2014)
  • Author(s): KUBO Masato
  • Organizer: France-Japan Immunology meeting
  • Place of Presentation: Cassis, France
  • Year and Date: 2014-10-22 – 2014-10-23
  • Invited
• [Presentation] Influenza virus vaccination effectively induces the protective antibody response independent on germinal centers (2014)
  • Author(s): KUBO Masato
  • Organizer: DRFG IMMUNOLOGY SEMINAR
  • Place of Presentation: Berlin, German
  • Year and Date: 2014-09-12
  • Invited
• [Presentation] Notch regulates reciprocal expression of CCR7 versus CXCR5 to control central memory T cell generation (2014)
  • Author(s): KUBO Masato
  • Organizer: The 2st. International Immunological Memory and Vaccine Forum
  • Place of Presentation: La Jolla, San Diego, CA USA
  • Year and Date: 2014-08-24 – 2014-08-25
  • Invited
• [Presentation] インフルエンザ感染の分子基盤 (2014)
  • Author(s): 久保允人
  • Organizer: 生命医科学研究所 ヒト疾患モデル研究センター 動物実験棟竣工記念シンポジウム
  • Place of Presentation: 東京理科大学野田キャンパス 薬学部講堂
  • Year and Date: 2014-07-12
  • Invited
• [Presentation] 好塩基球とナチュラルヘルパー細胞によるアレルギー性気道炎症の制御 (2014)
  • Author(s): 久保允人
  • Organizer: 第79回サイトカイン・インターフェロン学会
  • Place of Presentation: 北大医学部講堂 札幌
  • Year and Date: 2014-06-19 – 2014-06-20
  • Invited
• [Presentation] Cytokine regulation of antibody responses in influenza virus infection (2014)
  • Author(s): KUBO Masato
  • Organizer: Tsinghua University IMMUNOLOGY SEMINAR
  • Place of Presentation: Beijing
  • Year and Date: 2014-05-12
  • Invited
• [Presentation] Understanding a role of cytokine signaling in homeostatic skin regulation (2014)
  • Author(s): KUBO Masato
  • Organizer: Shanghai Immunodermatology Forum 2014
  • Place of Presentation: Shanghai
  • Year and Date: 2014-05-10
  • Invited