The role of Peyer's patch dendritic cells and macropahges in regulation of mucosal immune responses

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07631
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: KANAYA TAKASHI 国立研究開発法人理化学研究所, 生命医科学研究センター, 副チームリーダー (20553829)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 樹状細胞 / パイエル板 / 腸管免疫

Outline of Final Research Achievements

PPs take up antigens through M cells distributed in follicle-associated epithelium (FAE) covering PP lymphoid follicles, from which the antigens are transferred to dendritic cells (DCs) located in subepithelial dome (SED) for subsequent T cell-priming. Accumulating evidence indicates that SED-DCs have unique functions other than priming T cells to facilitate mucosal immune responses. We have previously shown that SED-DCs express IL-22 binding protein (IL-22BP), allowing an efficient antigen-uptake into PPs. Here we identified that RelB and C/EBPa were preferentially expressed by SED-DCs in murine PPs. RelB-deficiency silenced the expression of IL-22BP by SED-DCs. On the other hand, C/EBPa-deficiency decreased the expression of Lysozyme by SED-DCs, causing the increased invasion of orally administered pathogenic bacteria into PPs and mesenteric lymph nodes. Our findings demonstrate that RelB and C/EBPa regulate the development of SED-DCs, and contribute to the mucosal host defense.

Free Research Field

腸管免疫

Academic Significance and Societal Importance of the Research Achievements

パイエル板のSED領域には樹状細胞、リンパ球、自然リンパ球などの免疫細胞の他、ストロマ細胞や上皮細胞など非免疫細胞が集積し、複雑な微小環境形成している。この微小環境は腸管免疫を制御する上で重要な領域であると考えられているが、それぞれの細胞の機能不全モデルを確立することは困難であったことから、微小環境形成の分子メカニズムには不明な点が多い。本研究によってSED領域樹状細胞の機能制御機構の一端が明らかとなった。本研究成果はSED-DCを標的とした腸管免疫制御方法の開発に繋がると期待される。