Critical role of plasmacytoid dendritic cells in induction of oral tolerance

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15194
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: University of Miyazaki
• Principal Investigator: Takagi Hideaki 宮崎大学, 医学部, 助教 (10719628)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 形質細胞様樹状細胞 / 経口免疫寛容 / 粘膜免疫 / 制御性T細胞

Outline of Final Research Achievements

Exposure to dietary constituents through the mucosal surface of the gastrointestinal tract generates oral tolerance that prevents deleterious T cell-mediated immunity. While oral tolerance is an active process that involves the emergence of CD4+Foxp3+ regulatory T (Treg) cells in gut-associated lymphoid tissues (GALT) for the suppression of effector T (Teff) cells, how antigen (Ag)-presenting cells (APCs) initiate this process remains unclear. In this study, we sought to determine the role of plasmacytoid dendritic cells (pDCs), known as unconventional type APCs, in the establishment of oral tolerance. In conclusion, we report that gastrointestinal pDC-mediated tolerogenesis through de novo generation of CD4+Foxp3+ iTreg cells impacts the induction of oral tolerance leading to the abortive allergic responses.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究課題の意義として、これまで未知であった『腸管適応免疫応答の制御機構』に関する“pDC機能”の重要性が解明されることから新たな概念が提唱され、当該分野の発展に積極的に貢献できることが挙げられる。
さらに“pDC機能”に関する生物製剤などの分子標的創薬の研究開発が、ヒトpDCの生体内動態に基づいた腸管免疫疾患の病勢診断法とともに革新的な分子標的治療法の確立、ならびに感染症への新規経口粘膜ワクチンの開発を導くことが強く期待される。