Analysis on the mechanism of immune regulation by plasmacytoid dendritic cells in the development of autoimmune diseases

• Project/Area Number: 15K19134
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: University of Miyazaki
• Principal Investigator: Takagi Hideaki 宮崎大学, 医学部, 助教 (10719628)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 形質細胞様樹状細胞 / I型インターフェロン / 自己免疫疾患 / 炎症反応 / Toll様受容体 / I型IFN

Outline of Final Research Achievements

Plasmacytoid dendritic cells (pDCs) are important for the innate and adaptive immune responses by producing robust type-I interferon (IFN-I) through the toll-like receptor (TLR)-mediated signaling. However, how pDCs control TLR-mediated immune responses that cause autoimmunity remains unclear. In this study, we demonstrated a critical function of pDCs in the induction of TLR7-mediated innate and adaptive immune responses that cause autoimmunity using gene-modified mice with impaired expression of Siglec-H and selective ablation of pDCs. Our findings reveal that pDCs provide an essential link between TLR7-mediated innate and adaptive immunity for the initiation of IFN-I-associated autoimmune inflammation.

Research Products

• [Journal Article] Selective depletion of basophils ameliorates immunoglobulin E-mediated anaphylaxis (2017)
  • Author(s): Nakamura, T., Fukaya, T., Uto, T., Takagi, H., Arimura, K., Tono, T., and Sato, K.
  • Journal Title: Biochem. Biophys. Rep. Volume: 9 Pages: 29-35
  • DOI: 10.1016/j.bbrep.2016.11.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation (2017)
  • Author(s): Arimura, K., Takagi, H., Uto, T., Fukaya, T., Nakamura, T.,Choijookhuu, N., Hishikawa,Y. Yamashita,Y., and Sato, K.
  • Journal Title: Mucosal Immunol. Volume: 印刷中 Issue: 4 Pages: 957-970
  • DOI: 10.1038/mi.2016.96
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Plasmacytoid dendritic cells orchestrate TLR7-mediated innate and adaptive immunity for the initiation of autoimmune inflammation (2016)
  • Author(s): Hideaki Takagi, Keiichi Arimura, Tomofumi Uto, Tomohiro Fukaya, Takeshi Nakamura, Narantsog Choijookhuu, Yoshitaka Hishikawa, Katsuaki Sato
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 24477-24477
  • DOI: 10.1038/srep24477
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Tolerogenesis of gastrointestinal plasmacytoid dendritic cells impacts the induction of oral tolerance (2017)
  • Author(s): 高木秀明、宇都倫史、深谷知宏、奈須遵太、福井丈仁、宮永宜明、有村慶一、中村雄、佐藤克明
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] Plasmacytoid dendritic cells orchestrate TLR7-mediated innate and adaptive immunity for the initiation of autoimmune inflammation (2016)
  • Author(s): 高木秀明、有村慶一、宇都倫史、深谷知宏、中村雄、佐藤克明
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄
  • Year and Date: 2016-12-05
• [Presentation] Critical role of plasmacytoid dendritic cells in the initiation of toll-like receptor 7-mediated autoimmune inflammation (2015)
  • Author(s): 高木秀明、有村慶一、宇都倫史、深谷知宏、中村雄、佐藤克明
  • Organizer: 日本免疫学会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-11-18