Analysis of the role of DCIR2 in the function of CD4+conventional dendritic cells

• Project/Area Number: 25293117
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: University of Miyazaki
• Principal Investigator: Sato Katsuaki 宮崎大学, 医学部, 教授 (40301147)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 樹状細胞 / 自然免疫 / 適応免疫 / T細胞 / 機能抑制分子

Outline of Final Research Achievements

Here, we show that DCIR2 is a regulatory receptor for the activation of CD4+cDCs that impairs inflammation and T-cell immunity. Dcir2-/-CD4+cDCs show enhanced cytokine production and T-cell priming following TLR-mediated activation. Furthermore, Dcir2-/- mice exhibit TLR-mediated hyperinflammation. Upon antigenic immunization,Dcir2-/- mice show not only augmented T-cell responses but also progressive autoimmune pathogenesis. Thus, our findings highlight roles of Clec4A4 in regulation of the function of CD4+cDCs for control of the magnitude and quality of immune response.

Research Products

• [Int'l Joint Research] Inserm(France)
• [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] Critical roles of a dendritic cell subset expressing a chemokine receptor, XCR1 (2013)
  • Author(s): C. Yamazaki, M. Sugiyama, T. Ohta, H. Hemmi, E. Hamada, I. Sasaki, Y. Fukuda, T. Yano, M. Nobuoka, T. Hirashima, A. Iizuka, K. Sato, T. Tanaka, K. Hoshino, T. Kaisho
  • Journal Title: J. Immunol Volume: 190 Issue: 12 Pages: 6071-6082
  • DOI: 10.4049/jimmunol.1202798
  • Peer Reviewed
• [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回日本免疫学会総会
  • Place of Presentation: 札幌コンベンションセンター（北海道、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: 京都府京都市国立京都国際会館
  • 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: 京都府京都市国立京都国際会館
  • 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: 京都府京都市国立京都国際会館
  • 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: 京都府京都市国立京都国際会館
  • 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/
• [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/