Elucidation of differentiation and function of M cell in the airway

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07239
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Keio University
• Principal Investigator: Shunsuke Kimura 慶應義塾大学, 薬学部(芝共立), 准教授 (40444525)
• Co-Investigator(Kenkyū-buntansha): 久本 芽璃 北海道大学, 歯学研究院, 助教 (00754920)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: M細胞 / 呼吸器 / インフルエンザ

Outline of Final Research Achievements

Microfold (M) cells residing in the follicle-associated epithelium of mucosa-associated lymphoid tissues are specialized for sampling luminal antigens to initiate mucosal immune responses. In the past decade, RANKL-RANK signaling is essential for M-cell differentiation from the intestinal stem cells. However, the molecular characterization and differentiation mechanisms of M cells in the lower respiratory tract remain to be fully elucidated. Here we identified a progenitor cells which is differentiated to M cells by RANKL-RANK signaling. Furthermore, influenza infection differentiated the progenitor cells into functional M cells that efficiently ingest inhaled microparticles. We further confirmed that M cell induction by RANKL administration is suppressed in the progenitor cell-specific RANK deficient mice. Our research shed light on the new role of airway epithelial cells in the respiratory diseases.

Free Research Field

粘膜免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究はこれまで腸管で発展した粘膜免疫研究を呼吸器へと発展させたものである。これまで、下気道にM細胞が存在するという報告はなく新規性の高い成果である。さらには、その分化機構の解明、前駆細胞の同定に至り、それらの知見を基にM細胞欠損マウスの作製に成功している。
呼吸器疾患は生活の質へ与える影響が大きい。さらに、呼吸器感染症は致死率が高いだけではなく、伝播力が強く社会的な影響も大きい。本研究の成果を基に、今後呼吸器の粘膜免疫応答、感染機構が明らかになることで、将来的な予防法、治療方法の開発につながる。