Analysis of functions of a receptor tyrosine kinase selectively expressed in plasmacytoid dendritic cells.

• Project/Area Number: 26461465
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kagawa University
• Principal Investigator: Hoshino Katsuaki 香川大学, 医学部, 教授 (50324843)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 形質細胞様樹状細胞 / Ⅰ型インターフェロン / 全身性エリテマトーデス / Ｉ型インターフェロン

Outline of Final Research Achievements

We have demonstrated that an Ephrin receptor tyrosine kinase is selectively expressed in mouse plasmacytoid dendritic cells (pDCs) by use of a specific monoclonal antibody. When we incubate pDCs in vitro in the presence or absence of this monoclonal antibody, then stimulate with Toll-like receptor 7(TLR7) or TLR9 ligands, we have found that pDC produce comparable levels of cytokines including interferon-alpha. We have also found that pDCs normally developed in Flt3 ligand-induced bone marrow derived dendritic cells cultured in the presence of this monoclonal antibody. In order to analyze the function of the Ephrin receptor tyrosine kinase in mouse plasmacytoid dendritic cells, we have established two lines of knockout mouse. We are planning to analyze the phenotype of pDCs in these knockout mice.

Research Products

• [Journal Article] In vivo ablation of dendritic cell subset expressing the chemokine receptor XCR1. (2016)
  • Author(s): H. Hemmi, K. Hoshino, T. Kaisho.
  • Journal Title: Methods Mol Biol. Volume: 1423 Pages: 247-53
  • DOI: 10.1007/978-1-4939-3606-9_17
  • ISBN: 9781493936045, 9781493936069
  • Peer Reviewed
• [Journal Article] Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis. (2016)
  • Author(s): Ohta T, Sugiyama M, Hemmi H, Yamazaki C, Okura S, Sasaki I, Fukuda Y, Orimo T, Ishii KJ, Hoshino K, Ginhoux F, Kaisho T.
  • Journal Title: Scientific Reports Volume: 162 Issue: 1 Pages: 23505-23505
  • DOI: 10.1038/srep23505
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node (2016)
  • Author(s): Kitano M., Yamazaki C., Takumi A., Ikeno T., Hemmi H., Takahashi N., Shimizu K., Fraser S. E., Hoshino K., Kaisho T. and Okada T.
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 113 Issue: 4 Pages: 1044-1049
  • DOI: 10.1073/pnas.1513607113
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Antigen-specific cytotoxic T lymphocytes target airway CD103(+) and CD11b(+) dendritic cells to suppress allergic inflammation (2016)
  • Author(s): Daniels N. J., Hyde E., Ghosh S., Seo K., Price K. M., Hoshino K., Kaisho T., Okada T. and Ronchese F.
  • Journal Title: Mucosal immunology Volume: 9 Issue: 1 Pages: 229-239
  • DOI: 10.1038/mi.2015.55
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Limitation of immune tolerance-inducing thymic epithelial cell development by Spi-B-mediated negative feedback regulation. (2014)
  • Author(s): Akiyama, N., Shinzawa, M., Miyauchi, M., Yanai, H., Tateishi, R., Shimo, Y., Ohshima, D., Matsuo, M., Sasaki. I., Hoshino, K., Wu, G., Yagi, S., Inoue, J., Kaisho, T. and Akiyama, T.
  • Journal Title: J. Exp. Med. Volume: 211 Issue: 12 Pages: 2425-2438
  • DOI: 10.1084/jem.20141207
  • Peer Reviewed / Open Access
• [Journal Article] Single-Cell Imaging of Caspase-1 Dynamics Reveals an All-or-None Inflammasome Signaling Response. (2014)
  • Author(s): Liu, T., Yamaguchi, Y., Shirasaki, Y., Shikada, K., Yamagishi, M., Hoshino, K., Kaisho, T., Takemoto, K., Suzuki, T., Kuranaga, E., Ohara, O., Miura, M.
  • Journal Title: Cell Reports Volume: 8 Issue: 4 Pages: 974-982
  • DOI: 10.1016/j.celrep.2014.07.012
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 自然免疫受容体による樹状細胞活性化メカニズムの解析 (2017)
  • Author(s): 星野克明
  • Organizer: 2017肝免疫フォーラム
  • Place of Presentation: 芝パークホテル(東京都)
  • Year and Date: 2017-02-04
  • Invited
• [Presentation] 結核菌感染における初期免疫応答 (2015)
  • Author(s): 財賀大行、星野克明
  • Organizer: 第14回 四国免疫フォーラム
  • Place of Presentation: 愛媛大学医学部（愛媛県・松山市）
  • Year and Date: 2015-06-20
• [Presentation] 教育講演１-自然免疫受容体による樹状細胞活性化メカニズムの解析- (2014)
  • Author(s): 星野克明
  • Organizer: 第66回 日本皮膚科学会西部支部学術大会
  • Place of Presentation: 高松市
  • Year and Date: 2014-11-08
  • Invited