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Analysis of mucosal tolerance by regulatory T cell in chronic otitis media

Research Project

Project/Area Number 16K11187
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionOita University

Principal Investigator

Hirano Takashi  大分大学, 医学部, 講師 (20305056)

Co-Investigator(Kenkyū-buntansha) 川野 利明  大分大学, 医学部, 助教 (30633424)
鈴木 正志  大分大学, 医学部, 教授 (60211314)
Research Collaborator SUZUKI MASASHI  大分大学, 医学部, 教授 (60211314)
KAWANO TOSHIAKI  大分大学, 医学部, 助教 (30633424)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords制御性T細胞 / 粘膜免疫 / 免疫寛容 / B細胞 / 鼻粘膜 / 脾臓 / Bリンパ球 / 頸部リンパ節 / インフルエンザ菌 / 制御性T細胞細胞 / ヘルパーT細胞 / サイトカイン / 慢性中耳炎
Outline of Final Research Achievements

We investigated the effect of regulatory T cell (Treg) on B cell immune responses against outer membrane protein (OMP) from NTHi in vitro. Mice were vaccinated intranasally with OMP , and mononuclear cells (MNCs) were collected from the nasal mucosa, Tregs and helper T cells (Th) were isolated from the spleens of those mice. Three different cell culture groups were allocated: MNCs co-cultured with Tregs, or with Th cells, and MNCs cultured alone, respectively. At 24 and 72 hours after cell culture, cytokine levels were determined by ELISA. CD69 or CD80 expressions on B2 cells were detected by flow cytometryic analysis. IL-10 levels were significantly higher in Treg and Th groups than in the control group. The ratio of CD80+B220+ B2 cells was higher in the control group than in the Treg and Th groups during incubation. Tregs and Th cells may partially inhibit B cell functions, such as T cell activation. These inhibitory effects may be related to IL-10.

Academic Significance and Societal Importance of the Research Achievements

マウス慢性中耳炎由来の制御性T細胞を用いた検討は試料サイズが少ないため、脾臓由来の制御性T細胞やhelper T細胞によるマウス鼻粘膜由来B細胞における影響について検討を行った。現在まで、上気道粘膜由来B細胞におけるT細胞の関与についてin vitroでの解析の報告は少なく、今回は慢性感染と制御性T細胞の関与が上気道においても起こりえる可能性が示唆され、制御性T細胞のB細胞における抗体産生能に与える直接的な抑制効果よりも、特にT-B細胞間の相互作用の抑制効果が上気道粘膜における免疫寛容に関わっていることが示唆された。制御性T細胞は、慢性気道感染における新しい治療標的になるかもしれない。

Report

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

    (5 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (3 results)

  • [Journal Article] Interaction between regulatory T cells and antibody producing B cells for the immune responses at the upper respiratory mucosae against nontypeable Haemophilus influenza-in vitro assay model-2019

    • Author(s)
      Hirano T., Kadowaki Y., Matsunaga T., Yoshinaga K., Kawano T., Moriyama M., Suzuki M.
    • Journal Title

      Annals of Otology, Rhinology and Laryngology

      Volume: in press

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Monophosphoryl lipid A enhances nontypeable Haemophilus influenzae-specific mucosal and systemic immune responses by intranasal immunization2017

    • Author(s)
      Taro Iwasaki, Takashi Hirano, Satoru Kodama, Yoshinori Kadowaki, Munehito Moriyama, Toshiaki Kawano, Masashi Suzuki
    • Journal Title

      International Journal of Pediatric Otorhinolaryngology

      Volume: 97 Pages: 5-12

    • DOI

      10.1016/j.ijporl.2017.03.018

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 経鼻粘膜免疫後の頸部リンパ節に対する制御性T細胞が与える影響2018

    • Author(s)
      平野 隆,川野利明,松永崇志,門脇嘉宣、児玉 悟、鈴木正志
    • Organizer
      日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 経鼻粘膜免疫後の頸部リンパ節に対する制御性T細胞が与える影響2018

    • Author(s)
      平野 隆、川野利明、松永崇志、門脇嘉宣、児玉 悟、鈴木正志
    • Organizer
      日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 慢性中耳炎における制御性T細胞免疫寛容機序に対するin vitroでの解析2017

    • Author(s)
      平野 隆、川野利明、松永崇志、門脇嘉宣、児玉 悟、鈴木正志
    • Organizer
      日本耳科学会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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