Comprehensive understanding of M cells, unique intestinal epithelial cells specialized for luminal particulate antigen uptake

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08836
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: Sato Shintaro 大阪大学, 微生物病研究所, 特任准教授(常勤) (80447333)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 粘膜免疫 / M細胞

Outline of Final Research Achievements

We show that mouse allograft inflammatory factor 1 (Aif1) is expressed by M cells and contributes to M-cell transcytosis. FAE in Aif1－/－ mice has suppressed uptake of particles and commensal bacteria, compared with wild-type mice. Translocation of Yersinia enterocolitica, but not of Salmonella enterica serovar Typhimurium, leading to the generation of antigen-specific IgA antibodies, is also diminished in Aif1-deficient mice. Although β1 integrin, which acts as a receptor for Y. enterocolitica via invasin protein, is expressed on the apical surface membranes of M cells, its active form is rarely found in Aif1－/－ mice. These findings show that Aif1 is important for bacterial and particle transcytosis in M cells.

Free Research Field

粘膜免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究成果として、M細胞の機能発現に直接関わる分子としてAif1を同定し、M細胞におけるその機能、分子メカニズムを世界に先駆けて報告した。Aif1はM細胞の外来抗原取り込み能に直接関与していることから、Aif1の機能を調節することが出来れば、食物抗原やアレルゲン、病原性微生物の侵入を一過性にコントロールすることが可能となる。したがって、Aif1をターゲットとした薬剤の開発は、効果的な経口粘膜免疫寛容の誘導や腸管感染症の予防につながるものと考えられる。