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Study on oral mucosal immune regulation on the axis of activated vitamin D3

Research Project

Project/Area Number 19H03823
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionTohoku University

Principal Investigator

Sugawara Shunji  東北大学, 歯学研究科, 教授 (10241639)

Co-Investigator(Kenkyū-buntansha) 黒石 智誠  東北大学, 歯学研究科, 講師 (30400261)
多田 浩之  東北大学, 歯学研究科, 講師 (70431632)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
KeywordsビタミンD3 / 口腔免疫 / 粘膜免疫 / 免疫応答 / 口腔粘膜
Outline of Research at the Start

口腔粘膜は常に飲食物などの抗原にさらされているが、これらに対するアレルギーや炎症反応は通常起きない。一方、微生物感染に対して防御機構を発揮する、という相反する重要な機能をもつが、その誘導のメカニズムは未解決な部分が多い。また、唾液の主要抗体IgAは口腔の防御機構に重要であるが、その産生機構は十分に分かっていない。本研究は、ステロイドホルモン様の特性をもつ栄養素 活性型ビタミンD3(VD3)を基軸として、口腔粘膜の免疫応答調節機構の解明を目指す。本研究により、骨代謝で中心的な役割をもつ活性型VD3の口腔粘膜免疫、さらには全身の粘膜免疫に関する新たな学術基盤を構築する。

Outline of Final Research Achievements

This study was aimed to elucidate effects of activated vitamin D3 (VD3) on oral mucosal immune system. We first address the outcome of VD3 supplementation of sublingual immunotherapy (SLIT) in a murine delayed-type hypersensitivity (DTH) model. SLIT with VD3 significantly inhibited DTH response after the second challenge. Adoptive transfer of regulatory T (Treg) cells from mice treated with SLIT with VD3 exhibited therapeutic effects on OVA-DTH. Transcriptome analysis of Treg cells revealed that SLIT with VD3 generated functionally different Treg cells with altered gene expression profile. In the vitamin D3 deficient mice, expression of genes which are essential for IgA class switch from IgM, was markedly down-regulated. Taken together, these results suggest that VD3 play as important role for control of oral mucosal immune responses.

Academic Significance and Societal Importance of the Research Achievements

本研究は、“口腔(舌下)粘膜の免疫学的特性”を世界に先駆けて明らかにするという学術的基盤を構築するだけでなく、患者に負担をかけずに行えるSLITの効果を格段に向上させる基礎的研究基盤を提示するという点で、社会的にも大きな意義のある研究である。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (5 results)

All 2022 2021 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Remarks (3 results)

  • [Journal Article] Differential expression of CD11c defines two types of tissue-resident macrophages with different origins in steady-state salivary glands2022

    • Author(s)
      Lu Lu, Toshinobu Kuroishi, Yukinori Tanaka, Mutsumi Furukawa, Tomonori Nochi, Shunji Sugawara
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 931-931

    • DOI

      10.1038/s41598-022-04941-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] P2 purinergic receptor signaling and interleukin-1 synergistically induce interleukin-6 production in a human oral squamous carcinoma cell line2021

    • Author(s)
      Shishido Kaori、Kuroishi Toshinobu、Sugawara Shunji
    • Journal Title

      Journal of Oral Biosciences

      Volume: 63 Issue: 1 Pages: 80-90

    • DOI

      10.1016/j.job.2021.01.004

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Remarks] 東北大学大学院歯学研究科・歯学部 エコロジー歯学講座 口腔分子制御学分野

    • URL

      http://www.dent.tohoku.ac.jp/field/biology/05/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 東北大学大学院歯学研究科エコロジー歯学講座口腔分子制御学分野

    • URL

      http://www.oral-immunology.dent.tohoku.ac.jp/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 東北大学大学院歯学研究科口腔生物学講座口腔分子制御学分野

    • URL

      http://www.oral-immunology.dent.tohoku.ac.jp/index.html

    • Related Report
      2019 Annual Research Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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