Molecular mechanism of antigen transcytosis by M cells mediated by a novel identified M-cell specific molecule.

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23842
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Nobuhide Kobayashi 金沢大学, 医学系, 助教 (30712799)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: M細胞 / 樹状細胞 / ボツリヌス毒素

Outline of Final Research Achievements

M cells are specialized epithelial cells covered on the surface of mucosal lymphoid tissues, and transcytose intraluminal antigens to induce immune responses. On the other hand, M cells also serve as a route of entry for pathogenic agents such as botulinum toxin. However, the molecular mechanism of transcytosis by M cells remains unclear. In this study, we focused on a Pleckstrin homology domain-containing molecule (M-Plek), which is highly expressed in M cells. M-Plek-deficient mice were more sensitive to botulinum toxin than wild-type mice. In addition, we developed in vitro M-cell culture system using monolayer-cultured intestinal organoids to quantify transcytosis activity.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

M細胞による抗原輸送の分子機構には不明な点が多く、その解明は粘膜ワクチンなどへの応用に直結する。本研究で開発した単層培養オルガノイドにM細胞を誘導しトランスサイトーシス機能を定量的に評価する実験系は、M細胞トランスサイトーシスの分子機構の解明に有用なツールであると考えられる。今後、本実験系を用いてM-Plekやその他の輸送関連分子の寄与を解析する。また、本研究の結果、M-Plekはボツリヌス毒素に対して防御的に機能することが示唆された。今後詳細なメカニズムを解明することでボツリヌス症発症機構の解明にも寄与できると考えられる。