Analysis and characterization of corticoid-resistant t-cells

• Project/Area Number: 24790830
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital
• Principal Investigator: KOUYAMA Satoshi 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), その他部局等, 研究員 (20626783)
• Co-Investigator(Kenkyū-buntansha): 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長 (80251247)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 閉塞性肺疾患 / 免疫アレルギー学

Research Abstract

The understanding of the steroid-resistant mechanism of the T-cell level to characterize severe asthma is important as a premise of the treatment intervention. For the purpose of performing a preclinical study, we established a steroid-resistant asthmatic model. Steroid sensitivity evaluation was done using the steroid sensitivity of the in vitro T-cell clone and T-cell clone transfer mice asthma model (in vivo). By the administration of dexamethasone (Dex), lymphocyte count and eosinophil count in BALF of mice transfected with steroid-sensitive clone, was reduced in a dose-dependent manner. On the other hand, there was no significant reduction in the case where it is transferred with steroid-resistant clones. Namely, it was able to confirm that steroid sensitivity and resistance in the culture system (in vitro) accorded with the sensitivity in the asthma model (in vivo).

Research Products

• [Journal Article] A contraction assay system using primary cultured mouse bronchial smooth muscle cells (2013)
  • Author(s): Kouyama, S., Ohtomo-Abe, A., Kitamura, N., Kaminuma, O., and Mori, A
  • Journal Title: Int. Arch. Allergy Immunol Volume: 161 (Suppl 1) Pages: 93-97
• [Journal Article] A contraction assay system using primary cultured mouse bronchial smooth muscle cells. (2013)
  • Author(s): Kouyama S, Otomo-Abe A, Kitamura N, Kaminuma O, Mori A.
  • Journal Title: Int Arch Allergy Immunol. Volume: 161 Suppl 2 Issue: Suppl. 2 Pages: 93-7
  • DOI: 10.1159/000350366
  • Peer Reviewed
• [Journal Article] A contraction assay system using primary cultured mouse bronchial smooth muscle cells (2013)
  • Author(s): Satoshi Kouyama, Akemi Otomo-Abe, Noriko Kitamura, Osamu Kaminuma, Akio Mori
  • Journal Title: International Archives of Allergy and Immunology Volume: 161
  • Peer Reviewed
• [Journal Article] Murine T cell-derived contractile activity for bronchial smooth muscle cells (2012)
  • Author(s): Abe, A., Koyama, S., Ohtomo, T., Kitamura, N., Kaminuma, O., and Mori, A
  • Journal Title: Int. Arch. Allergy Immunol Volume: 158 (Suppl 1) Pages: 7-10
• [Presentation] 2014. Establishment and treatment of a steroid resistant asthma model by adoptive transfer of helper T cell clones (2014)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., 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: 2014 American Academy of Allergy, Asthma, and Immunology Annual meeting.
  • Place of Presentation: San Diego(J. Allergy Clin. Immunol. 131 (2):128)
• [Presentation] 2014. Broncho-constriction mediated by activated T cells in humans and mice (2014)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Abe,A., Ohtomo, T.,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: Airwai Vista 2014
  • Place of Presentation: Seoul( Respirology19(Suppl. 1):18 )
• [Presentation] 2014. Study on T cell-inducedbronchoconstrictioninvivo andinvitro (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: 2014World Asthma COPD Forum 2014
  • Place of Presentation: New York
• [Presentation] 2014. Airflow limitation caused by activated T cells (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: European Academy of Allergy and Clinical Immunology Congress 2014, Final program
  • Place of Presentation: Copenhagen
• [Presentation] 2014.Tcell induced-bronchoconstriction invitro 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., andKaminuma, O
  • Organizer: Collegium Internationale Allergologicum 2014 Meeting Final program
  • Place of Presentation: Petersberg
• [Presentation] 2014. Analysis of T cell-dependent bronchoconstriction (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: Asian Pacific Society of Respirology 2014 Congress Final program
  • Place of Presentation: Bali
• [Presentation] 2013. Tcell-inducedlate phase asthmatic response in mice (2013)
  • Author(s): Mori, A., Kouyama, S., Abe, A., Yamaguchi, M., Iijima, Y., Mitsui, C., Oshikata, C., Tanimoto, H., Fukutomi, Y., Sekiya, K., Taniguchi, M., Maeda, Y., Ohtomo, M., Hasegawa, M., Akiyama, K., Ohtomo, T., andKaminuma,O
  • Organizer: 2013 American Academy of Allergy, Asthma, and Immunology Annual meeting.
  • Place of Presentation: San Antonio(J. Allergy Clin. Immunol. 131 (2):128 )
• [Presentation] 2013. Adoptive transfer of Th clones confer late-phase asthmatic response in mice (2013)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Itoh, J., Saito, N., 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., Ohtomo, T., and Kaminuma, O
  • Organizer: European Academy of Allergy and Clinical Immunology-World Allergy Organization World Allergy & Asthma Congress 2013, Final program
  • Place of Presentation: Milan(p.58)
• [Presentation] 2013. Broncho-constriction mediated by T cells -an adoptive transfer model (2013)
  • Author(s): Mori, A., Kouyama, S., Yamaguchi, M., Iijima, Y., Abe,A., Ohtomo, T.,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: 2013 Asia Pacific Congress of Allergy and Clinical Immunology
  • Place of Presentation: Taipei(Allergy 68 (Suppl 98):15)
• [Presentation] 非アトピー型喘息のマウスモデル作成と解析 (2013)
  • Author(s): 神山智、大友暁美、大友隆之、山口美也子、飯島葉、森晶夫
  • Organizer: 日本職業・環境アレルギー学会 2013
  • Place of Presentation: 相模原(抄録集p.41)
• [Presentation] 非アトピー型喘息のマウスモデル作成と解析 (2013)
  • Author(s): 神山 智、大友暁美、大友隆之、山口美也子、飯島 葉、森 晶夫
  • Organizer: 日本職業・環境アレルギー学会2013
  • Place of Presentation: 相模原
• [Presentation] 培養マウス気管支平滑筋細胞ゲルを用いたT細胞クローン由来気管支収縮活性の評価 (2012)
  • Author(s): 神山智、安部暁美、山口美也子、飯島葉、榎美香、大友隆之、神沼修、森晶夫
  • Organizer: アレルギー・好酸球研究会2012
  • Place of Presentation: 東京(抄録集p.22)
  • Year and Date: 2012-06-23
• [Presentation] 2012. Treatment for steroid-resistant asthma model (2012)
  • Author(s): Mori, A., Abe, A., Kouyama, S., Mitsui, C., Oshikata, C., Tanimoto, H., Fukutomi, Y., Sekiya, K., Taniguchi, M., Ohtomo, M., Maeda, Y., Hasegawa, M., Akiyama, K., Ohtomo, T., and Kaminuma, K
  • Organizer: European Academy of Allergy and Clinical Immunology Congress 2012. Programme
  • Place of Presentation: Geneva(p.56 )
• [Presentation] 2012. Blocking costimulatory signal for treatingsteroid-resistantasthmamodel (2012)
  • Author(s): Mori, A., Abe, A., Kouyama, S., Yamaguchi, M., Enoki, M., Iijima, Y., Mitsui, C., Oshikata, C., Tanimoto, H., Fukutomi, Y., Sekiya, K., Taniguchi, M., Ohtomo, M., Maeda, Y., Hasegawa, M., Akiyama, K., Ohtomo, T., and Kaminuma, K
  • Organizer: European Respiratory Society 2012 Annual Congress. Final programme
  • Place of Presentation: Vienna( p.292 )
• [Presentation] 2012. Steroid responsiveness of peripheral blood T cells derived from steroid sensitive, steroid dependent, and steroid resistant asthmatics, and induction of steroid resistance by costimulatory signal (2012)
  • Author(s): Mori, A., Abe, A., Kouyama, S., Yamaguchi, M., Enoki, M., Iijima, Y., Mitsui, C., Oshikata, C., Tanimoto, H., Fukutomi, Y., Sekiya, K., Taniguchi, M., Ohtomo, M., Maeda, Y., Hasegawa, M., Akiyama, K., Ohtomo, T., and Kaminuma, K
  • Organizer: European Respiratory Society 2012 Annual Congress. Programme
  • Place of Presentation: Gothenburg( p.14)