The chronic mechanisms of oral mucosal disease and new treatment targeting co-stimulatory molecules on dendritic cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K24138
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Juntendo University (2021); Tohoku University (2020); Tokyo Medical and Dental University (2019)
• Principal Investigator: Nishii Emi 順天堂大学, 医学部, 助教 (00848674)
• Project Period (FY): 2019-08-30 – 2022-03-31
• Keywords: 炎症 / T細胞 / 制御性T細胞 / IFN-gamma

Outline of Final Research Achievements

In this study, we investigated the interaction between IFN-gamma-expressing T cells and regulatory T cells(Tregs) using chemotherapy-induced oral mucositis (OM) model.　In OM-tissue, infiltration of CD4T cells as well as innate immune cells was observed, and about 20% of CD4T cells expressed IFN-gamma. In IFN-gamma-deficient mice, mucosal inflammation was reduced and the Treg ratio was significantly increased. It was suggested that suppression of IFN-gamma expression may strongly tilt the inflammatory / anti-inflammatory balance toward "anti-inflammatory".

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、抗癌剤誘導性口腔粘膜炎マウスモデルを用いて、特に粘膜に浸潤するT細胞に着目し、研究を遂行した。炎症の増幅に関わるIFN-gamma発現T細胞と、炎症抑制に関わる制御性T細胞の相互作用ついて検討する中で、IFN-gammaの発現抑制がTreg比率を上昇させ、粘膜炎症を改善できる可能性を見いだした。抗癌剤により重傷化する粘膜炎は、癌治療の継続にも関わる重要な問題であり、IFN-gammaの局所的な発現抑制が粘膜炎を改善する新規治療法となりうる可能性が見いだされた。