Molecular mechanisms underlying differentiation of intestinal M cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08457
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Hokkaido University
• Principal Investigator: Kimura Shunsuke 北海道大学, 医学研究院, 助教 (40444525)
• Research Collaborator: KOBAYASHI nobuhide
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: M細胞 / パイエル板 / Sox8 / IgA

Outline of Final Research Achievements

Microfold (M) cells residing in the follicle-associated epithelium (FAE) of the gut-associated lymphoid tissue are specialized for antigen uptake to initiate mucosal immune responses. The molecular machinery and biological significance of M cell differentiation, however, remain to be fully elucidated. Here, we demonstrate that Sox8, a member of the SRY-related HMG box transcription factor family, is specifically expressed by M cells in the intestinal epithelium. Sox8 directly binds the promoter region of Gp2 to increase Gp2 expression, which is the hallmark of functionally mature M cells. Furthermore, genetic deletion of Sox8 causes a marked decrease in the number of mature M cells, resulting in reduced antigen uptake in Peyer's patches. Consequently, juvenile Sox8-deficient mice showed attenuated germinal center reactions and antigen-specific IgA responses. These findings indicate that Sox8 plays an essential role in the development of M cells to establish mucosal immune responses.

Free Research Field

組織細胞学

Academic Significance and Societal Importance of the Research Achievements

M細胞分化を制御する機構には不明な点が多かった。本研究によってSox8がM細胞の機能的な成熟に関与していることが明らかになった。Sox8によって制御される分子の解析を今後続けていくことで、M細胞がどのようにして抗原取り込み能を獲得していくかが明らかになると期待できる。Sox8欠損マウスでは特に離乳後のIgA抗体産生能力が低下していた。これは生後の免疫を獲得するために必要であることから、今後の乳幼児医療に有用な知見となる。