Analysis on the mechanism of immune regulation by CD4+ conventional dendritic cells in the development of autoimmune diseases

• Project/Area Number: 26860337
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: University of Miyazaki
• Principal Investigator: FUKAYA Tomohiro 宮崎大学, 医学部, 助教 (20624323)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 樹状細胞 / 自己免疫 / 免疫寛容

Outline of Final Research Achievements

Dcir2-/- CD4+ cDCs showed a higher secretion of proinflammatory cytokines and an enhanced T-cell priming after stimulation with TLR ligands than wild-type (WT) CD4+ cDCs. Furthermore, Dcir2-/- mice exhibit a hyperinflammatory response associated with the excessive production of cytokines. On antigenic immunization, Dcir2-/- mice showed a more enhanced autoimmune pathogenesis than WT mice. Thus, our findings suggest that DCIR2 provides an inhibitory signal for the fine-tuning of the function of CD4+ cDCs to maintain immune homeostasis and prevent autoimmune diseases.

Research Products

• [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] 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] Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T cell immunity (2016)
  • Author(s): Tomofumi Uto, Tomohiro Fukaya, Hideaki Takagi, Keiichi Arimura, Takeshi Nakamura, Naoya Kojima, Bernard Malissen, and Katsuaki Sato
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 1-15
  • DOI: 10.1038/ncomms11273
  • Peer Reviewed / Open Access / Int'l Joint Research / 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] Clec4A4 is a regulatory receptor for the Toll-like receptor-mediated activation of dendritic cells (2016)
  • Author(s): 深谷知宏、宇都倫史、高木秀明、有村慶一、中村雄、小島直也、佐藤克明
  • Organizer: 第４5回日本免疫学会学術集会
  • Place of Presentation: 宜野湾市
  • Year and Date: 2016-12-05
• [Presentation] Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation (2016)
  • Author(s): 有村慶一、高木秀明、宇都倫史、深谷知宏、中村雄、佐藤克明
  • Organizer: 第４5回日本免疫学会学術集会
  • Place of Presentation: 宜野湾市
  • Year and Date: 2016-12-05
• [Presentation] Selective depletion of basophils ameliorates immunoglobulin E-mediated anaphylaxis (2016)
  • Author(s): 中村雄、深谷知宏、宇都倫史、高木秀明、有村慶一、佐藤克明
  • Organizer: 第４5回日本免疫学会学術集会
  • Place of Presentation: 宜野湾市
  • Year and Date: 2016-12-05
• [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回日本免疫学会学術集会
  • Place of Presentation: 宜野湾市
  • Year and Date: 2016-12-05
• [Presentation] Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T cell immunity (2016)
  • Author(s): 宇都倫史、深谷知宏、高木秀明、有村慶一、中村雄、小島直也、佐藤克明
  • Organizer: 第４5回日本免疫学会学術集会
  • Place of Presentation: 宜野湾市
  • Year and Date: 2016-12-05
• [Presentation] Pivotal roles of type I interferon and costimulation signals in the development of imiquimod-induced psoriasiform dermatitis in mice (2015)
  • Author(s): 深谷知宏、宇都倫史、高木秀明、有村慶一、中村雄、佐藤克明
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 2015-11-18
• [Presentation] Crucial role of plasmacytoid dendritic cells in the development of acute DSS-induced colitis through the regulation of intestinal inflammation (2015)
  • Author(s): 有村慶一、高木秀明、宇都倫史、深谷知宏、中村雄、佐藤克明
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 2015-11-18
• [Presentation] DCIR2 is a regulatory receptor for the activation of conventional dendritic cells that impairs inflammation and T-cell immunity in vivo (2015)
  • Author(s): 宇都倫史、深谷知宏、高木秀明、有村慶一、中村雄、佐藤克明
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 2015-11-18
• [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、深谷知宏、宇都倫史、中村雄、佐藤克明
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 2015-11-18
• [Presentation] Selective depletion of basophils ameliorates passive anaphylaxis (2015)
  • Author(s): 中村雄、深谷知宏、宇都倫史、高木秀明、有村慶一、佐藤克明
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 2015-11-18
• [Presentation] DCIR2 is an inhibitory receptor for the TLR-mediated activation of conventional dendritic cells that regulates inflammation and T cell immunity in vivo (2014)
  • Author(s): 宇都倫史、深谷知宏、高木秀明、有村慶一、佐藤克明
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Pivotal role of plasmacytoid dendritic cells in the development of imiquimod-induced psoriasiform dermatitis in mice (2014)
  • Author(s): 高木秀明、有村慶一、深谷知宏、宇都倫史、佐藤克明
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Conditional ablation of CD205+ conventional dendritic cells impacts the regulation of antibacterial T cell immunity in vivo (2014)
  • Author(s): 深谷知宏、宇都倫史、高木秀明、有村慶一、佐藤克明
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Critical role of plasmacytoid dendritic cells in the development of acute DSS-induced colitis (2014)
  • Author(s): 有村慶一、高木秀明、深谷知宏、宇都倫史、佐藤克明
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Remarks] 宮崎大学医学部医学科感染症学講座免疫学分野
  • URL: http://www.med.miyazaki-u.ac.jp/meneki/