Investigation on T cell-dependent, IgE-independent bronchoconstriction mechanism

• Project/Area Number: 26461497
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital
• Principal Investigator: MORI AKIO 独立行政法人国立病院機構(相模原病院臨床研究センター), 先端技術開発研究部, 部長 (80251247)
• Co-Investigator(Kenkyū-buntansha): 神山 智 独立行政法人国立病院機構(相模原病院臨床研究センター), 先端技術開発研究部, 研究員 (20626783) [Withdrawn]
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 喘息 / T細胞 / 平滑筋 / 遅発型反応 / 喘息モデル / アレルギー / ぜんそく反応 / メディエータ / 喘息反応

Outline of Final Research Achievements

T cell-induced bronchoconstriction in asthma is studied in the present study. Antigen-specific T cell clones were established from PBMC obtained from asthmatic donors, and the culture supernatants of T cell clones were analyzed in terms of human bronchial smooth muscle cells-embedded collagen gels. In addition, murine antigen-specific T cell clones and murine asthma model was established to clarify immunological mechanisms of T cell-induced bronchoconstriction. Lastly, we tried to analyze guinea pig bronchial ring for pharmacological characterization of this response.

Research Products

• [Journal Article] Critical role of CD44 in antigen-induced Th2- but not Th17-madiated murine airway inflammation (2017)
  • Author(s): Nishimura, T., Katoh, S., Mori, A., Ohtomo, T., Saeki, M., Hiroi, T., and Kaminuma, O.
  • Journal Title: Allergol. Int. Volume: 65 Issue: Supplement.1 Pages: 559-561
  • DOI: 10.1016/j.alit.2016.04.010
  • NAID: 130005418881
  • ISSN: 1323-8930, 1440-1592
  • Year and Date: 2017-12-11
  • Peer Reviewed / Open Access
• [Journal Article] Increased serum IL-17A and Th2 cytokine levels in patients with severe uncontrolled asthma (2017)
  • Author(s): Hasegawa, T., Uga, H., Mori, A., and Kurata, H.
  • Journal Title: Eur. Cytokine Netw. Volume: -
  • Peer Reviewed
• [Journal Article] Hyper‐reactive cloned mice generated by direct nuclear transfer of antigen‐specific CD4+ T cells (2017)
  • Author(s): Kaminuma O, Katayama K, Inoue K, Saeki M, Nishimura T, Kitamura N, Shimo Y, Tofukuji S, Ishida S, Ogonuki N, Kamimura S, Oikawa M, Katoh S, Mori A, Shichijo M, Hiroi T, Ogura A
  • Journal Title: EMBO reports Volume: 印刷中 Pages: 885-893
  • DOI: 10.15252/embr.201643321
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Crosstalk between histamine and T cells in allergic diseases (2016)
  • Author(s): Saeki M, Nishimura T, Kaminuma O, Ohtsu H, Mori A and Hiroi T
  • Journal Title: Cur. Immunol. Rev. Volume: 12 Pages: 10-13
  • DOI: 10.2174/1573395511666150706180936
  • Peer Reviewed
• [Journal Article] アレルギー疾患各論 成人喘息 病因 (2016)
  • Author(s): 森 晶夫
  • Journal Title: 日本医師会雑誌 Volume: 145 Pages: 118-120
• [Journal Article] 重症喘息における好酸球性炎症 (2016)
  • Author(s): 森 晶夫
  • Journal Title: アレルギーの臨床 Volume: 36 Pages: 1353-1358
• [Journal Article] IL-5とアレルギー (2016)
  • Author(s): 神沼 修、森 晶夫
  • Journal Title: アレルギー・免疫 Volume: 23 Pages: 1478-1488
• [Journal Article] アレルギー性炎症におけるサイトカインの役割 (2016)
  • Author(s): 森 晶夫
  • Journal Title: アレルギー・免疫 Volume: 23 Pages: 1469-1470
• [Journal Article] 好酸球性多発血管炎性肉芽腫症 (2016)
  • Author(s): 谷口正実、濱田祐斗、福冨友馬、関谷潔史、粒来崇博、森 晶夫
  • Journal Title: アレルギーの臨床 Volume: 36 Pages: 1335-1339
• [Journal Article] Essential Contribution of CD4+ T Cells to Antigen-Induced Nasal Hyperresponsiveness in Experimental Allergic Rhinitis (2016)
  • Author(s): Nishimura, T., Kaminuma, O., Saeki, M., Kitamura, N., Matsuoka, K., Yoneyama, H., Mori, A., and Hiroi, T.
  • Journal Title: PLoS ONE Volume: １１
  • DOI: 10.1371/journal.pone.0146686
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 喘息の難治化をきたす基本病態 (2015)
  • Author(s): 森 晶夫
  • Journal Title: Respiratory Medical Research Volume: 3 Pages: 9-15
• [Journal Article] in vitro 抗原負荷とサイトカイン (2015)
  • Author(s): 森 晶夫
  • Journal Title: アレルギー・免疫 Volume: 22 Pages: 134-143
• [Journal Article] Food Allergen-induced IgE Response Mouse Model Created by Injection of <i>in vitro</i> Differentiated Th2 Cell Culture and Oral Antigen Intake (2014)
  • Author(s): Shibahara, K., Nakajima-Adachi, H., Kaminuma, O., Hiroi, T., Mori, A., and Hachimura, S.
  • Journal Title: Bioscience of Microbiota, Food and Health Volume: 33 Issue: 1 Pages: 41-46
  • DOI: 10.12938/bmfh.33.41
  • NAID: 130004562682
  • ISSN: 2186-3342
  • Peer Reviewed
• [Journal Article] Selective Suppression of Th2 Cell-Mediated Lung Eosinophilic Inflammation by Anti-Major Facilitator Super Family Domain Containing 10 Monoclonal Antibody (2014)
  • Author(s): Nishimura T, Saeki M, Motoi Y, Kitamura N, Mori A, Kaminuma O, Hiroi T.
  • Journal Title: Allergol. Int. Volume: 63 Suppl 1 Issue: Supplement.1 Pages: 29-35
  • DOI: 10.2332/allergolint.13-oa-0635 10.2332/allergolint.13-OA-0635
  • NAID: 130004477230
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Antigen-Induced Mixed and Separated Inflammation in Murine Upper and Lower Airways (2014)
  • Author(s): Saeki M, Nishimura T, Mori A, Kaminuma O, Hiroi T.
  • Journal Title: Allergol. Int. Volume: 63 Suppl 1 Issue: Supplement.1 Pages: 59-61
  • DOI: 10.2332/allergolint.13-le-0634 10.2332/allergolint.13-LE-0634
  • NAID: 130004477223
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] 吸入薬 (2014)
  • Author(s): 森 晶夫
  • Journal Title: アレルギー・免疫 Volume: 21 Pages: 82-91
• [Journal Article] 喘息とサイトカイン研究の進歩 新たな治療戦略について (2014)
  • Author(s): 森 晶夫
  • Journal Title: infoAllergy Volume: 69 Pages: 5-5
• [Journal Article] 共刺激調節薬とアレルギー (2014)
  • Author(s): 森 晶夫
  • Journal Title: アレルギーの臨床 Volume: 34 Pages: 1263-1266
• [Presentation] Blockade of Costimulatory Signal Enhanced Glucocorticoid Suppression of T Cell-Induced Eosinophilia (2017)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Ohtomo-Abe, A., Kamide, Y., Hayashi, H., Watai, K., Mitsui, C., Sekiya, K., Tsuburai, T., Taniguchi, M., Ohtomo, T., Kaminuma, O.
  • Organizer: 2017 American Academy of Allergy Asthma & Immunology Annual Meeting
  • Place of Presentation: Atlanta
  • Year and Date: 2017-03-03
  • Int'l Joint Research
• [Presentation] Effect of costimulatory signal blockade on steroid resistant asthma (2016)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Ohtomo-Abe, A., Kamide, Y., Hayashi, H., Watai, K., Mitsui, C., Sekiya, K., Tsuburai, T., Fukutomi, Y., Taniguchi, M., Ohtomo, T., and Kaminuma, O.
  • Organizer: 21st Congress of Asian Pacific Society of Respirology
  • Place of Presentation: Bangkok
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Synergistic suppression of T cell-induced eosinophilia by CTLA4-Ig and glucocorticoid in murine asthma model (2016)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Ohtomo-Abe, A., Kamide, Y., Hayashi, H., Watai, K., Mitsui, C., Sekiya, K., Tsuburai, T., Fukutomi, Y., Taniguchi, M., Ohtomo, T., and Kaminuma, O.
  • Organizer: European Respiratory Society International Congress 2016
  • Place of Presentation: London
  • Year and Date: 2016-09-02
  • Int'l Joint Research
• [Presentation] Effect of CTLA4-Ig on steroid resistant asthma model (2016)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Ohtomo-Abe, A., Kamide, Y., Hayashi, H., Watai, K., Mitsui, C., Sekiya, K., Tsuburai, T., Fukutomi, Y., Taniguchi, M., Ohtomo, T., Kaminuma, O.
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: Melbourne
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] T cell-induced bronchoconstriction in the mice - a model for late asthmatic response (2016)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Ohtomo-Abe, Kamide, Y., Hayashi, H., Watai, K., Mitsui, C., Sekiya, K., Tsuburai, T., Fukutomi, Y., Taniguchi, M., Ohtomo, T., and Kaminuma, O.
  • Organizer: European Academy of Allergy and Clinical Immunology Congress 2016
  • Place of Presentation: Vienna
  • Year and Date: 2016-06-11
  • Int'l Joint Research
• [Presentation] Role of costimulatory signals in the induction of T cell steroid resistance in asthma (2016)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Ohtomo-Abe, A., Kinoshita, A., Kamide, Y., Hayashi, H., Watai, K., Mitsui, C., Oshikata, C., Sekiya, K., Tsuburai, T., Ohtomo, M., Fukutomi, Y., Taniguchi, M., Ohtomo, T., and Kaminuma, O.
  • Organizer: 31th Symposium of the Collegium Internationale Allergologicum
  • Place of Presentation: Charleston
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Control of steroid responsiveness of Th cells in asthma (2016)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Ohtomo-Abe, A., Kinoshita, A., Kamide, Y., Hayashi, H., Watai, K., Mitsui, C., Oshikata, C., Sekiya, K., Tsuburai, T., Ohtomo, M., Fukutomi, Y., Taniguchi, M., Ohtomo, T., and Kaminuma, O.
  • Organizer: 2016 American Academy of Allergy, Asthma, and Immunology Annual Meeting
  • Place of Presentation: Los Angels
  • Year and Date: 2016-03-04
  • Int'l Joint Research
• [Presentation] Acidic conditions regulate mast cell migration and Fc epsilon RI-mediated cytokine production (2016)
  • Author(s): Kamide, Y., Ishizuka, T., Hayashi, H., Mitsui, C., Mori, A., Hisada, T., Dobashi, K., Okajima, F., Yamada, M., and Taniguchi, M.
  • Organizer: 2016 American Academy of Allergy, Asthma, and Immunology Annual Meeting
  • Place of Presentation: Los Angels
  • Year and Date: 2016-03-04
  • Int'l Joint Research
• [Presentation] Suppression of lipid mediators by the humanized anti-IgE antibody Omalizumab in aspirin-exacerbated respiratory disease (2016)
  • Author(s): Hayashi, H., Mitsui, C., Fukutomi, Y., Kajiwara, K., Watai, K., Kinoshita, A., Kamide, Y., Sekiya, K., Tsuburai, T., Mori, A., Akiyama, K., Hasegawa, Y., and Taniguchi, M.
  • Organizer: 2016 American Academy of Allergy, Asthma, and Immunology Annual Meeting
  • Place of Presentation: Los Angels
  • Year and Date: 2016-03-04
  • Int'l Joint Research
• [Presentation] Pharmacological characterization of T cell-induce bronchoconstriction response (2015)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Ohtomo-Abe, Saito, N., A., Kinoshita, A., Hayashi, H., Watarai, K., Mitsui, C., Oshikata, C., Sekiya, K., Tsuburai, T., Maeda, Y., Ohtomo, M., Fukutomi, Y., Taniguchi, M., Akiyama, K., Ohtomo, T., and Kaminuma, O.
  • Organizer: Asian Pacific Society of Respirology 2015 Congress
  • Place of Presentation: Kuala Lumpur
  • Year and Date: 2015-12-03
  • Int'l Joint Research
• [Presentation] Effects of LTRA on T cell-induced bronchoconstriction in the mice (2015)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Ohtomo-Abe, A., saito, N., Kinoshita, A., Hayashi, H., Watarai, K., Mitsui, C., Oshikata, C., Sekiya, K., Tsuburai, T., Maeda, Y., Ohtomo, M., Fukutomi, Y., Taniguchi, M., Akiyama, K., Ohtomo, T., and Kaminuma, O.
  • Organizer: European Respiratory Society International Congress 2015
  • Place of Presentation: Amsterdam
  • Year and Date: 2015-09-26
  • Int'l Joint Research
• [Presentation] T-cell dependent, steroid-resistant asthma model and its treatment by blocking costimulatory signal (2015)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Ohtomo-Abe, A., Saito, N, Kinoshita, A., Hayashi, H., Watarai, K., Mitsui, C., Oshikata, C., Sekiya, K., Tsuburai, T., Maeda, Y., Ohtomo, M., Fukutomi, Y., Taniguchi, M., Akiyama, K., Ohtomo, T., and Kaminuma, O
  • Organizer: World Immunoe Regulation Meeting IX
  • Place of Presentation: Davos, Switzerland
  • Year and Date: 2015-03-18 – 2015-03-21
• [Presentation] Pharmacological characterization of T cell-induce bronchoconstriction in the mice (2015)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Ohtomo-Abe, A., Saito, N, Kinoshita, A., Hayashi, H., Watarai, K., Mitsui, C., Oshikata, C., Sekiya, K., Tsuburai, T., Maeda, Y., Ohtomo, M., Fukutomi, Y., Taniguchi, M., Akiyama, K., Ohtomo, T., and Kaminuma, O.
  • Organizer: 2015 American Academy of Allergy, Asthma, and Immunology Annual meeting
  • Place of Presentation: Houston, USA
  • Year and Date: 2015-02-20 – 2015-02-24
• [Presentation] Costimulatory signal as a target for treating steroid resistant asthma (2015)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Ohtomo-Abe, A., Saito, N, Kinoshita, A., Hayashi, H., Watarai, K., Mitsui, C., Oshikata, C., Sekiya, K., Tsuburai, T., Maeda, Y., Ohtomo, M., Fukutomi, Y., Taniguchi, M., Akiyama, K., Ohtomo, T., and Kaminuma, O
  • Organizer: 7th Immunotherapeutics & Immunomonitoring Conference
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-01-29 – 2015-01-30
• [Presentation] Development and treatment of steroid resistant asthma model by adoptive transfer of murine helper T cell clones (2014)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Ohtomo, A., Ohtomo, T., Itoh, J., Hayashi, H., Watarai, K., Mitsui, C., Oshikata, C., Fukutomi, Y., Sekiya, K., Tsuburai, T., Maeda, Y., Ohtomo, M., Taniguchi, M., Akiyama, K., and Kaminuma, O.
  • Organizer: WAO Internal Scientific Conference 2014
  • Place of Presentation: Rio de Janeiro, Brazil
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] T cell induced-bronchoconstriction in vitro and in vivo (2014)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Abe, A., Ohtomo, T., Fukuhara, M., Itoh, J., Hayashi, H., Minami, T., Watarai, K., Mitsui, C., Oshikata, C., Tanimoto, H., Fukutomi, Y., Sekiya, K., Tsuburai, T., Taniguchi, M., Maeda, Y., Ohtomo, M., Hasegawa, M., Akiyama, K., and Kaminuma, O.
  • Organizer: Collegium Internationale Allergologicum 2014 Meeting
  • Place of Presentation: Petersberg, Germany
  • Year and Date: 2014-09-13 – 2014-09-18
• [Presentation] Airflow limitation caused by activated T cells (2014)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Abe-Ohtomo, A., Ohtomo, T., Fukuhara, M., Itoh, J., Hayashi, H., Minami, T., Watarai, K., Mitsui, C., Oshikata, C., Tanimoto, H., Fukutomi, Y., Sekiya, K., Tsuburai, T., Taniguchi, M., Maeda, Y., Ohtomo, M., Hasegawa, M., Akiyama, K., and Kaminuma, O.
  • Organizer: European Academy of Allergy and Clinical Immunology Congress 2014
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2014-06-07 – 2014-06-11
• [Presentation] Selective down-regulation of IL-2-mediated cytokine expression in human T cells by protein phosphatase 1 inhibitors (2014)
  • Author(s): Kaminuma, O., Kitamura, N., Mori, A., and Hiroi, T.
  • Organizer: EXPERIMENTAL BIOLOGY
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-04-30
• [Presentation] Study on T cell-induced bronchoconstriction in vivo and in vitro (2014)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Abe, A., Ohtomo, T., Fukuhara, M., Itoh, J., Hayashi, H., Minami, T., Watarai, K., Mitsui, C., Oshikata, C., Tanimoto, H., Fukutomi, Y., Sekiya, K., Tsuburai, T., Taniguchi, M., Maeda, Y., Ohtomo, M., Hasegawa, M., Akiyama, K., and Kaminuma, O.
  • Organizer: VII World Asthma Allergy & COPD Forum
  • Place of Presentation: New York, USA
  • Year and Date: 2014-04-26 – 2014-04-29
• [Book] Allergies: Current challenges and solutions, proceedings of the 30th Symposium of the Collegium Internationale Allergologicum (M. Maurer, and H. Behrendt eds.) (2016)
  • Author(s): Mori, A., Kouyama, S., Abe, A., Ohtomo, T., and Kaminuma, O.
  • Total Pages: 169
  • Publisher: Pancini Editore S.r.l., Pisa, Italy