Development of autovaccine for periodontal disease using human salivary exosomes with immune activity

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07162
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Teikyo Heisei University
• Principal Investigator: Ogawa Yuko 帝京平成大学, 薬学部, 准教授 (30267330)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 細胞外小胞 / 唾液 / LPS / マクロファージ / DPP IV

Outline of Final Research Achievements

Exosome-like extracellular vesicles (Exo) derived from human saliva is composed of both a membrane vesicle and an outer layer surrounding it. Salivary Exo contain LPS derived from oral bacteria and DPP IV as immunostimulators and activate macrophage (Mφ). In addition, Mφ activation by the dissociated outer layer were enhanced. CAP18, a LPS-binding protein, that is contained in salivary Exo is considered to function suppressively in Mφ activation. The outer layer of the Exo is easily degraded, while the vesicle including DPP IV were relatively stable. Therefore, the Exo adsorbs LPS and suppresses excessive activation of the immune system in the oral cavity. Enhanced immune activation may occur when the outer layer is dissociated from the Exo.

Free Research Field

衛生薬学

Academic Significance and Societal Importance of the Research Achievements

本研究で得られたLPS/DPP IV-Exoの構成成分、免疫系における機能、安定性に関する知見より、本Exoは口腔内から消化管内を通じて免疫系を制御するリソースとなることが期待できる。LPS/DPP IV-Exoは唾液中のLPSの10～20%を結合している。口腔内で本ExoはLPSを吸着し、免疫系の過剰な活性化を抑制しているが、消化管では消化に伴う外層の解離による免疫活性化が起こると考えられた。外層と本体の消化に伴う免疫系への作用を分子レベルで解明することで、外来性の病原体に対して免疫系を制御し、効率的な生体防御を行う機能的Exoを構築できる可能性がある。