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Detection of human TIM-4 on autoimmune and allergic diseases

Research Project

Project/Area Number 16K09924
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionJuntendo University

Principal Investigator

Akiba Hisaya  順天堂大学, 医学(系)研究科(研究院), 准教授 (60338316)

Co-Investigator(Renkei-kenkyūsha) HARADA norihiro  順天堂大学, 医学部, 准教授 (10465065)
ABE yoshiyuki  順天堂大学, 医学部, 助教 (10647027)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords免疫 / アレルギー / ぜんそく / 炎症 / 診断薬 / 免疫学 / 喘息 / アレルギー・ぜんそく
Outline of Final Research Achievements

T cell immunoglobulin and mucin domain (TIM)-4 plays essential roles in macrophage homeostasis. We have previously detected a soluble form of the extracellular domain of TIM-4 (sTIM-4) generated by proteolytic cleavage of mouse macrophages. sTIM-4 induced proinflammatory cytokine production by naive and IgE-stimulated mast cells. Thus, we measured the concentrations of sTIM-4 in patients with asthma in evaluated 125 adult patients with mild to severe asthma. The serum sTIM-4 levels were significantly higher in the asthmatic patients with step 5 treatment by Global Initiative for Asthma (GINA) as compared with the patients with GINA step 1 to 4 treatment. The data suggest that serum sTIM-4 may be associated with asthma severity and may have the potential to be used as biomarker in asthma.

Academic Significance and Societal Importance of the Research Achievements

遊離型TIM-4は多種の炎症性サイトカイン産生の誘導に働く。現在、TNF-αなど個々の炎症性サイトカインを標的にした抗体医薬品は実用されているが、多種の炎症性サイトカイン産生を総合的に根本から抑制することが可能になれば、個々の抗サイトカイン抗体療法に抵抗性を示す患者さんの治療に繋がると考えている。また抗TIM-4抗体による抗炎症作用は、喘息に留まらず、他の難治性慢性炎症疾患の新たな治療ターゲット分子になる可能性がある。また遊離型TIM-4は、補助診断あるいは治療効果や予後予測に際して有用なバイオマーカーになる可能性がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (27 results)

All 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] University of Maryland/The Washington University(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] University of Edinburgh(英国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Pusan National University(韓国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Characterization of tenascin-C as a novel biomarker for asthma: utility of tenascin-C in combination with periostin or immunoglobulin E2018

    • Author(s)
      Yasuda Mina、Harada Norihiro、Harada Sonoko、Ishimori Ayako、Katsura Yoko、Itoigawa Yukinari、Matsuno Kei、Makino Fumihiko、Ito Jun、Ono Junya、Tobino Kazunori、Akiba Hisaya、Atsuta Ryo、Izuhara Kenji、Takahashi Kazuhisa
    • Journal Title

      Allergy, Asthma & Clinical Immunology

      Volume: 14 Issue: 1 Pages: 72-72

    • DOI

      10.1186/s13223-018-0300-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination of TWEAK and TGF-β1 induces the production of TSLP, RANTES, and TARC in BEAS-2B human bronchial epithelial cells during epithelial-mesenchymal transition2018

    • Author(s)
      Matsuno Kei、Harada Norihiro、Harada Sonoko、Takeshige Tomohito、Ishimori Ayako、Itoigawa Yukinari、Katsura Yoko、Kodama Yuzo、Makino Fumihiko、Ito Jun、Atsuta Ryo、Akiba Hisaya、Takahashi Kazuhisa
    • Journal Title

      Experimental Lung Research

      Volume: 44 Issue: 7 Pages: 332-343

    • DOI

      10.1080/01902148.2018.1522558

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-TIM-3 Treatment Exacerbates Pulmonary Inflammation and Fibrosis in Mice.2017

    • Author(s)
      Isshiki T, Akiba H, Nakayama M, Harada N, Okumura K, Homma S, Miyake S.
    • Journal Title

      J Immunol

      Volume: 199 Issue: 11 Pages: 3733-3737

    • DOI

      10.4049/jimmunol.1700059

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective role of ICOS and ICOS Ligand in corneal transplantation and in maintenance of immune privilege2016

    • Author(s)
      Kunishige T, Taniguchi H, Terada M, Akiba H, Yagita H, Abe R, Hori J
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 57(15) Issue: 15 Pages: 6815-6823

    • DOI

      10.1167/iovs.16-20644

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] OX40L blockade protects against inflammation-driven fibrosis.2016

    • Author(s)
      Elhai M, Avouac J, Hoffmann-Vold AM, Ruzehaji N, Amiar O, Ruiz B, Brahiti H, Ponsoye M, Frechet M, Burgevin A, Pezet S, Sadoine J, Guilbert T, Nicco C, Akiba H, Heissmeyer V, Subramaniam A, Resnick R, Molberg O, Kahan A, Chiocchia G, Allanore Y.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 113 Issue: 27

    • DOI

      10.1073/pnas.1523512113

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Circulating levels of tenascin-C as type 2 biomarkers in the patients with asthma2018

    • Author(s)
      M. Asaji, N. Harada, S. Harada, A. Ishimori, Y. Katsura, Y. Itoigawa, K. Matsuno, F. Makino, J. Ito, J. Ono, K. Tobino, H. Akiba, R. Atsuta, K. Izuhara, K. Takahashi
    • Organizer
      第58回日本呼吸器学会会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Chitin Induced Airway Inflammation and Production of Prostaglandin E22018

    • Author(s)
      T. Takeshige, N. Harada, K. Matsuno, A. Ishimori, Y. Tanabe, H. Sasano, A. Nakamura, S. Harada, Y. Katsura, F. Makino, J. Ito, R. Atsuta, H. Akiba, K. Takahashi
    • Organizer
      第58回日本呼吸器学会会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 気管支喘息のバイオマーカーとしての血清テネイシンC値の可能性2018

    • Author(s)
      浅地美奈、原田紀宏、原田園子、石森絢子、桂蓉子、糸魚川幸成、松野圭、牧野文彦、伊藤潤、小野純也、飛野和則、秋葉久弥、熱田了、出原賢治、高橋和久
    • Organizer
      第67回日本アレルギー学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト気道上皮細胞におけるキチンによるPGE2産生誘導2018

    • Author(s)
      竹重智仁、原田紀宏、石森絢子、松野圭、原田園子、三道ユウキ、上田翔子、安部寿美子、中村愛、笹野仁史、田辺悠記、桂蓉子、牧野文彦、伊藤潤、秋葉久弥、熱田了、高橋和久
    • Organizer
      第67回日本アレルギー学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 免疫チェックポイントTIMの慢性炎症における働き2018

    • Author(s)
      秋葉久弥
    • Organizer
      第36回呼吸器・免疫シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Expression of TIM-4 in normal cornea and corneal grafts2018

    • Author(s)
      A. Takeda, H. Taniguchi, T. Kunishige, H. Akiba, H. Yagita, J. Hori
    • Organizer
      The Annual Meeting of the Association for Research in Vision and Ophthalmology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Circulating levels of soluble TIM-4 in the patients with asthma2018

    • Author(s)
      Yuki Tanabe, Hisaya Akiba, Norihiro Harada, Kei Matsuno, Jun Ito, Kazuhisa Takahashi, and Sachiko Miyake
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The effect of mepolizumab treatment in patients with severe asthma2017

    • Author(s)
      Yuuki Sandhu, Norihiro Harada, Kei Matsuno, Sonoko Harada, Tomohito Takeshige, Ayako Ishimori, Yoko Katsura, Fumihiko Makino, Jun Ito, Ryo Atsuta, Hisaya Akiba, Kazuhisa Takahashi
    • Organizer
      The 22nd Congress of the Asian Pacific Society of Respirology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Serum tenascin-C levels in patients with asthma2017

    • Author(s)
      Norihiro Harada, Mina Asaji, Sonoko Harada, Ayako Ishimori, Yoko Katsura, Yukinari Itoigawa, Kei Matsuno, Fumihiko Makino, Jun Ito, Junya Ono, Kazunori Tobino, Hisaya Akiba, Ryo Atsuta1, Kenji Izuhara, and Kazuhisa Takahashi
    • Organizer
      The 22nd Congress of the Asian Pacific Society of Respirology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] TWEAK and TGF-β induced chemokine production in human bronchial epithelial cells during epithelial mesenchymal transition2017

    • Author(s)
      Kei Matsuno, Norihiro Harada, Tomohito Takeshige, Ayako Ishimori, Yuki Tanabe, Hitoshi Sasano, Ai Nakamura, Yoko Katsura, Fumihiko Makino, Jun Ito, Ryo Atsuta, Hisaya Akiba, Kazuhisa Takahashi
    • Organizer
      The 22nd Congress of the Asian Pacific Society of Respirology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Chitin induced airway inflammation and production of prostaglandin E22017

    • Author(s)
      Tomohito Takeshige, Norihiro Harada, Kei Matsuno, Ayako Ishimori, Yuki Tanabe, Hitoshi Sasano, Ai Nakamura, Sonoko Harada, Yoko Katsura, Fumihiko Makino, Jun Ito, Ryo Atsuta, Hisaya Akiba, Kazuhisa Takahashi
    • Organizer
      The 22nd Congress of the Asian Pacific Society of Respirology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 上皮間葉転換が誘導された気道上皮細胞におけるケモカイン産生2017

    • Author(s)
      松野圭, 原田紀宏, 石森絢子, 竹重智仁, 桂蓉子, 三道ユウキ, 中村愛, 笹野仁史, 田辺悠記, 牧野文彦, 伊藤潤, 熱田了, 秋葉久弥, 高橋和久
    • Organizer
      第66回日本アレルギー学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 抗TIM-3抗体は死細胞貪食を阻害してブレオマイシン肺臓炎を悪化させる2017

    • Author(s)
      一色琢磨, 秋葉久弥,中山勝文, 原田紀宏, 奥村康, 三宅幸子, 本間栄
    • Organizer
      第21回東京呼吸病態研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] TWEAK enhances epithelial mesenchymal transition and chemokine production in human bronchial epithelial cells2017

    • Author(s)
      Kei Matsuno, Norihiro Harada, Itoigawa Yukinari, Tomohito Takeshige, Sonoko Harada, Ayako Ishimori, Yuki Tanabe, Yoko Katsura, Fumihiko Makino, Jun Ito, Ryo Atsuta, Hisaya Akiba, Kazuhisa Takahashi
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Anti-TIM-3 treatment exacerbates pulmonary inflammation and fibrosis in mice2017

    • Author(s)
      Takuma ISSHIKI, Hisaya AKIBA, Masafumi NAKAYAMA, Norihiro HARADA, Ko OKUMURA, Sachiko MIYAKE
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] TIM-3 regulates pulmonary fibrosis through apoptotic cell clearance2016

    • Author(s)
      ISSHIKI Takuma, AKIBA Hisaya, NAKAYAMA Masafumi, HARADA Norihiro, OKUMURA Ko, MIYAKE Sachiko
    • Organizer
      第45回日本免疫学会
    • Place of Presentation
      沖縄コンベンションセンター、ラグナガーデンホテル
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] OX40L BLOCKADE PROTECTS AGAINST SKIN AND LUNG INFLAMMATION-DRIVEN FIBROSIS2016

    • Author(s)
      M. Elhai, J. Avouac, A.-M. Hoffmann-Vold, J. Sadoine, T. Guilbert, H. Akiba, V. Heissmeyer, A. Subramaniam, R. Resnick, G. Chiocchia, Y. Allanore
    • Organizer
      欧州リウマチ学会 EULAR 2016
    • Place of Presentation
      London, UK
    • Year and Date
      2016-06-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 順天堂大学医学部免疫学

    • URL

      https://www.juntendo.ac.jp/graduate/laboratory/labo/meneki/home.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 順天堂大学医学部免疫学講座

    • URL

      http://www.juntendo.ac.jp/graduate/laboratory/labo/meneki/home.html

    • Related Report
      2017 Research-status Report 2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-07-19  

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