Analysis of dendritic cell function in immune responses

• Project/Area Number: 24590460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Wakayama Medical University (2014); Osaka University (2012-2013)
• Principal Investigator: HEMMI Hiroaki 和歌山県立医科大学, 先端医学研究所, 准教授 (20451924)
• Research Collaborator: FUKUDA Yuri ; TANAKA Yuriko
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 樹状細胞 / 免疫応答 / 免疫制御 / 腸管 / 炎症

Outline of Final Research Achievements

Dendritic cells are professional antigen presenting cells and consist of several subsets with specialized functions. A XC chemokine receptor 1 (XCR1) is selectively expressed on a dendritic cell subset showing a high ability to cross-present antigens to naive CD8 T cells. Conditional ablation of these XCR1+ dendritic cells in vivo are achieved by generation of gene modified mice in which the XCR1 gene was replaced with a gene coding for a fusion protein consisting of human diphtheria toxin receptor and fluorescent protein venus. In these mice, XCR1+ dendritic cells were transiently and conditionally ablated when diphtheria toxin was injected. Using this system, we found that cross-presentation as well as oral tolerance was impaired in the absence of XCR1+ dendritic cells in vivo. These results suggest that XCR1+ dendritic cells play important roles in induction of not only immune response but also immune tolerance.

Research Products

• [Journal Article] Homeostasis of thymus-derived Foxp3+ regulatory T cells is controlled by ultraviolet B exposure in the skin. (2014)
  • Author(s): S. Yamazaki, A. Nishioka, S. Kasuya, N. Ohkura, H. Hemmi, T. Kaisho, O. Taguchi, S. Sakaguchi, A. Morita
  • Journal Title: J Immunol Volume: 193(11) Issue: 11 Pages: 5488-97
  • DOI: 10.4049/jimmunol.1400985
  • Peer Reviewed
• [Journal Article] Olfactory plays a key role in spatiotemporal pathogenesis of cerebral malaria. (2014)
  • Author(s): H. Zhao, T. Aoshi, S. Kawai, Y. Mori, A. Konishi, M. Ozkan, Y. Fujita, Y. Haseda, M. Shimizu, M. Kohyama, K. Kobiyama, K. Eto, J. Nabekura, T. Horii, T. Ishino, M. Yuda, H. Hemmi, T. Kaisho, S. Akira, M. Kinoshita, K. Tohyama, Y. Yoshioka, K. J. Ishii, C. Coban
  • Journal Title: Cell Host Microbe Volume: 15 Issue: 5 Pages: 551-563
  • DOI: 10.1016/j.chom.2014.04.008
  • Peer Reviewed / Open Access
• [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
• [Journal Article] Spi-B is critical for plasmacytoid dendritic cell function and development (2012)
  • Author(s): Sasaki, K. Hoshino, T. Sugiyama, C. Yamazaki, T. Yano, A. Iizuka, H. Hemmi, T. Tanaka, M. Saito, M. Sugiyama, Y. Fukuda, T. Ohta, K. Sato, A. Ainai, T. Suzuki, H. Hasegawa, N. Toyama-Sorimachi, H. Kohara, T. Nagasawa, T. Kaisho
  • Journal Title: Blood Volume: 120 Issue: 24 Pages: 4733-4743
  • DOI: 10.1182/blood-2012-06-436527
  • Peer Reviewed
• [Presentation] Roles of Arginase I in Cholera toxin-induced production of proinflammatory cytokines. (2014)
  • Author(s): Sasaki I, Fukuda S, Orimo T, Hemmi H, Kaisho T.
  • Organizer: 第43回日本免疫学会総会・学術集会.
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Homeostasis of thymus-derived Foxp3+ regulatory T cells is controlled by ultraviolet B exposure in the skin. (2014)
  • Author(s): Yamazaki S, Nishioka A, Kasuya K, Ohkura N, Hemmi H, Kaisho T, Taguchi O, Sakaguchi S, Morita A.
  • Organizer: 第43回日本免疫学会総会・学術集会.
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] XCL1 and XCR1 are involved in intestinal immune homeostasis by dendritic cells. (2014)
  • Author(s): Ohta T, Okura S, Hemmi H, Sugiyama M, Sasaki I, Yamazaki C, Hoshino K, Kaisho T.
  • Organizer: 第43回日本免疫学会総会・学術集会.
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Function of XCR1-expressing dendritic cells in oral tolerance. (2013)
  • Author(s): Hemmi H, Sugiyama M, Ohta T, Sasaki I, Yamazaki C, Tanaka T, Hoshino K, Kaisho T.
  • Organizer: 第42回 日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉県）
• [Presentation] A novel mechanism to generate the intestinal intraepitherial T lymphocytes by XCR1-expressing dendritic cells (2013)
  • Author(s): Ohta T, Hemmi H, Yamazaki C, Sugiyama M, Sasaki I, Hoshino K, Kaisho T.
  • Organizer: 第42回 日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉県）
• [Presentation] Analysis of in vivo function of XC chemokine receptor-expressing dendritic cells. (2012)
  • Author(s): Sugiyama, M. et al.
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場・神戸国際展示場・神戸ポートピアホテル （兵庫県）
• [Presentation] Spi-B is critical for plasmacytoid dendritic cell development in bone marrow. (2012)
  • Author(s): Sasaki, I. et al.
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場・神戸国際展示場・神戸ポートピアホテル （兵庫県）
• [Presentation] Ablation of a dendritic cell subset expressing XC chemokine receptor 1 in vivo (2012)
  • Author(s): Hemmi, H. et al.
  • Organizer: The 12th International Symposium on Dendritic Cells
  • Place of Presentation: EXCO （大邱, 韓国）