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Elucidation of the role of innate lymphoid cells in periodontitis

Research Project

Project/Area Number 22K20983
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0907:Oral science and related fields
Research InstitutionTohoku University

Principal Investigator

Kondo Takeru  東北大学, 歯学研究科, 助教 (40964226)

Project Period (FY) 2022-08-31 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords自然リンパ球 / 歯周炎 / 自然リンパ球 ILC
Outline of Research at the Start

近年,クローン病や喘息などの免疫疾患において,T細胞やB細胞とは別の新たな細胞集団である,自然リンパ球 Innate lymphoid cell (ILC) が重要な役割を果たすことが報告され,粘膜組織の炎症反応において注目を集めている.これまでに我々はマウスにおける歯周炎確立期にILCが出現し,他の免疫細胞を活性化する遺伝子を多く発現する知見を得ている.そこで申請者は,ILCが口腔粘膜の慢性炎症疾患である歯周炎において重要な役割を果たし,歯周炎メカニズム解明の新たな鍵となると考えた.本研究では遺伝子改変マウスを用いて歯周炎を惹起させ,ILCが歯周炎進行に与える影響を明らかにする.

Outline of Final Research Achievements

In the gingiva of wild-type mice with periodontitis, the number of type 3 innate lymphocytes (ILC3s) increased, and the ILC3s strongly expressed Il17a, which promotes bone resorption. In addition, the number of osteoclasts in the alveolar bone decreased, and alveolar bone resorption was suppressed in ILC knockout mice. These results suggest that ILC3s would promote alveolar bone resorption through activation of osteoclasts. Single-cell RNA-sequencing analysis indicated that the specific gingival fibroblast population might regulate ILC3s through various potential molecules in periodontitis-induced gingiva.
Taken together, this study demonstrated that ILC3s may activate by gingival fibroblasts induced alveolar bone resorption via osteoclasts.

Academic Significance and Societal Importance of the Research Achievements

ILCが発見されて以来,ヒト歯周炎患者の歯周組織におけるILCの存在を示した論文が最近発表されているものの、その病理学的役割を示した研究はいまだ見当たらない.本研究では,口腔粘膜においてILC3sが破骨細胞を介して歯槽骨吸収を引き起し,歯周炎進行を促進する可能性を示した.このことから,ILC3sを歯周炎治療の新たな標的とすることで,新規歯周炎治療法開発に大きく貢献できると思われる.また,歯周組織における免疫細胞としてILCが注目されることで,抜歯窩治癒など様々な歯周組織の免疫機構解明の起爆剤となる可能性がある.

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (11 results)

All 2024 2023 2022

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Innate immune regulation in dental implant osseointegration2024

    • Author(s)
      Kondo Takeru、Yamada Masahiro、Egusa Hiroshi
    • Journal Title

      Journal of Prosthodontic Research

      Volume: 68 Issue: 4 Pages: 511-521

    • DOI

      10.2186/jpr.JPR_D_23_00198

    • ISSN
      1883-1958, 1883-9207
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Zinc- and fluoride-releasing bioactive glass as a novel bone substitute2024

    • Author(s)
      Kondo Takeru、Otake Koki、Kakinuma Hiroaki、Sato Yumi、Ambo Sara、Egusa Hiroshi
    • Journal Title

      Journal of Dental Research

      Volume: In press

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mouse gingival single-cell transcriptomic atlas identified a novel fibroblast subpopulation activated to guide oral barrier immunity in periodontitis2023

    • Author(s)
      Kondo Takeru、Gleason Annie、Okawa Hiroko、Hokugo Akishige、Nishimura Ichiro
    • Journal Title

      eLife

      Volume: 12 Pages: 88183-88183

    • DOI

      10.7554/elife.88183

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Incomplete Polymerization of Dual-Cured Resin Cement Due to Attenuated Light through Zirconia Induces Inflammatory Responses2023

    • Author(s)
      Kondo Takeru、Kakinuma Hiroaki、Fujimura Kanna、Ambo Sara、Otake Koki、Sato Yumi、Egusa Hiroshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 12 Pages: 9861-9861

    • DOI

      10.3390/ijms24129861

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current perspectives of residual ridge resorption: Pathological activation of oral barrier osteoclasts2023

    • Author(s)
      Takeru Kondo, Keiichi Kanayama, Hiroshi Egusa, Ichiro Nishimura.
    • Journal Title

      Journal of Prosthodontic Research

      Volume: 67 Issue: 1 Pages: 12-22

    • DOI

      10.2186/jpr.JPR_D_21_00333

    • NAID

      130008162258

    • ISSN
      1883-1958, 1883-9207
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cyclic pressure-induced cytokines from gingival fibroblasts stimulate osteoclast activity: Clinical implications for alveolar bone loss in denture wearers2023

    • Author(s)
      Akashi Yoshihiro、Nagasaki Atsuhiro、Okawa Hiroko、Matsumoto Takuya、Kondo Takeru、Yatani Hirofumi、Nishimura Ichiro、Egusa Hiroshi
    • Journal Title

      Journal of Prosthodontic Research

      Volume: 67 Issue: 1 Pages: 77-86

    • DOI

      10.2186/jpr.JPR_D_21_00238

    • NAID

      130008162256

    • ISSN
      1883-1958, 1883-9207
    • Related Report
      2022 Research-status Report
  • [Journal Article] Oral microbial extracellular DNA initiates periodontitis through gingival degradation by fibroblast-derived cathepsin K in mice2022

    • Author(s)
      Kondo Takeru、Okawa Hiroko、Hokugo Akishige、Shokeen Bhumika、Sundberg Oskar、Zheng Yiying、McKenna Charles E.、Lux Renate、Nishimura Ichiro
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 962-962

    • DOI

      10.1038/s42003-022-03896-7

    • Related Report
      2022 Research-status Report
  • [Journal Article] Mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ) revealed by targeted removal of legacy bisphosphonate from jawbone using competing inert hydroxymethylene diphosphonate2022

    • Author(s)
      Okawa Hiroko、Kondo Takeru、Hokugo Akishige、Cherian Philip、Campagna Jesus J、Lentini Nicholas A、Sung Eric C、Chiang Samantha、Lin Yi-Ling、Ebetino Frank H、John Varghese、Sun Shuting、McKenna Charles E、Nishimura Ichiro
    • Journal Title

      eLife

      Volume: 11 Pages: 112-112

    • DOI

      10.7554/elife.76207

    • Related Report
      2022 Research-status Report
  • [Journal Article] Effect of Calcium Ion Supplementation on Oral Microbial Composition and Biofilm Formation In Vitro2022

    • Author(s)
      Shokeen Bhumika、Pham Elaine、Esfandi Julia、Kondo Takeru、Okawa Hiroko、Nishimura Ichiro、Lux Renate
    • Journal Title

      Microorganisms

      Volume: 10 Issue: 9 Pages: 1780-1780

    • DOI

      10.3390/microorganisms10091780

    • Related Report
      2022 Research-status Report
  • [Presentation] 口腔粘膜における特定歯肉線維芽細胞集団による免疫機構2023

    • Author(s)
      近藤 威、Ichiro Nishimura、江草 宏
    • Organizer
      日本補綴歯科学会第132回学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] プラーク由来細胞外DNAに着目した歯周病リスク診断の新機軸2023

    • Author(s)
      近藤威,江草宏
    • Organizer
      日本歯科医学会 第38回歯科医学を中心とした総合的な研究を推進する集い
    • Related Report
      2022 Research-status Report

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Published: 2022-09-01   Modified: 2025-01-30  

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