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Development of a novel approach for infected wounds focusing on lymphocyte function

Research Project

Project/Area Number 19K19494
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 58050:Fundamental of nursing-related
Research InstitutionTohoku University

Principal Investigator

Tanno Hiromasa  東北大学, 医学系研究科, 助教 (10755664)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords創傷治癒 / 感染 / NKT細胞 / α-GalCer / リンパ球 / 白血球 / 感染創
Outline of Research at the Start

慢性創傷のほぼ100%は感染を有しており、治癒が難治化する。感染創のケアとして、洗浄、デブリードマンなどが選択されるが、宿主免疫機能の低下により、感染が再発し治癒が進行しない。その解決策として、リンパ球を活性化し、創傷ケアと同時に宿主免疫を活性化することで、効率的に慢性創傷を治癒に導けると考えた。
本研究では、リンパ球を活性化するα-GalCerを感染創マウスモデル(創+細菌感染)および、重症感染創モデル(創+細菌感染+糖尿病)マウスモデルに投与し、リンパ球の活性化が慢性創傷の細菌感染 (バイオフィルム形成)、治癒速度に与える影響を解明することより、宿主免疫を増強する新規ケア技術の確立を目指す。

Outline of Final Research Achievements

Bacteria are detected in more than 90% of chronic wounds such as pressure ulcers and diabetic leg ulcers, and Pseudomonas aeruginosa is one of the most frequently detected bacteria. In this study, we analyzed the effect of NKT cell activation on the elimination of P. aeruginosa in wounds.
Administration of α-GalCer, a specific activator of NKT cells, resulted in significantly decreased the number of live colonies in the wounded tissues on days 5 and 7 after P. aeruginosa inoculation, and significantly increased the number of neutrophils on day 3. IFN-γ, IL-22, IL-23, IL-12p70, and S100A9 production were significantly higher in α-GalCer-treated group than in vehicle-treated group. These results suggest that iNKT cells promote P. aeruginosa clearance during skin wound healing.

Academic Significance and Societal Importance of the Research Achievements

現在、細菌感染・バイオフィルム形成が疑われる慢性創傷のケアとして、洗浄、銀イオン含有ドレッシング材などが選択され、これらは創部の細菌数を減らすことに主眼を置いている。本研究は、宿主免疫を標的とした新しい創傷ケア技術の確立を目指すものである。本研究により、宿主免疫活性化が創部細菌数を減らすことが明らかとなり、新しい創傷ケア技術となる可能性を示した。この宿主免疫を標的としたケア技術は、救済できる慢性創傷を増やす可能性がある。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (6 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (3 results) (of which Invited: 1 results)

  • [Journal Article] Contribution of Invariant Natural Killer T Cells to the Clearance of Pseudomonas aeruginosa from Skin Wounds2021

    • Author(s)
      Tanno Hiromasa、Kanno Emi、Sato Suzuna、Asao Yu、Shimono Mizuki、Kurosaka Shiho、Oikawa Yukari、Ishi Shinyo、Shoji Miki、Sato Ko、Kasamatsu Jun、Miyasaka Tomomitsu、Yamamoto Hideki、Ishii Keiko、Imai Yoshimichi、Tachi Masahiro、Kawakami Kazuyoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 8 Pages: 3931-3931

    • DOI

      10.3390/ijms22083931

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distinct Roles for Dectin-1 and Dectin-2 in Skin Wound Healing and Neutrophilic Inflammatory Responses2021

    • Author(s)
      Yamaguchi Kenji、Kanno Emi、Tanno Hiromasa、Sasaki Ayako、Kitai Yuki、Miura Takayuki、Takagi Naoyuki、Shoji Miki、Kasamatsu Jun、Sato Ko、Sato Yuka、Niiyama Momoko、Goto Yuka、Ishii Keiko、Imai Yoshimichi、Saijo Shinobu、Iwakura Yoichiro、Tachi Masahiro、Kawakami Kazuyoshi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 141 Issue: 1 Pages: 164-176

    • DOI

      10.1016/j.jid.2020.04.030

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Defect of interferon γ leads to impaired wound healing through prolonged neutrophilic inflammatory response and enhanced MMP-2 activation.2019

    • Author(s)
      Kanno E, Tanno H, Masaki A, Sasaki A, Sato N, Goto M, Shisai M, Yamaguchi K, Takagi N, Shoji M, Kitai Y, Sato K, Kasamatsu J, Ishii K, Miyasaka T, Kawakami K, Imai Y, Iwakura Y, Maruyama R, Tachi M, Kawakami K.
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 20(22) Issue: 22 Pages: 5657-5657

    • DOI

      10.3390/ijms20225657

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Dectin-2シグナルを介した皮膚創傷治癒遅延へのNatural Killer T細胞欠損の影響2020

    • Author(s)
      丹野寛大, 菅野恵美, 佐々木綾子, 佐藤光, 笠松純, 石井恵子, 館正弘, 川上和義
    • Organizer
      第4回東北医真菌研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Dectin-2シグナルを介した皮膚創傷治癒へのNatural Killer T細胞欠損の影響2020

    • Author(s)
      丹野寛大, 菅野恵美, 佐々木綾子, 黒坂志歩, 及川ゆかり, 石井恵子, 川上和義, 館正弘
    • Organizer
      第50回日本創傷治癒学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 創傷治癒機構に対する宿主免疫に注目して ~看護学、形成外科学、免疫学の融合~2019

    • Author(s)
      丹野寛大
    • Organizer
      第49回日本創傷治癒学会
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-04-18   Modified: 2022-01-27  

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