Elucidation of the novel developmental pathway of NKT cells from thymic CD4, CD8-double-negative precursors

• Project/Area Number: 21790485
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: DASHTSOODOL Nyambayar 独立行政法人理化学研究所, 免疫制御研究グループ, 客員研究員 (50443057)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ナチュラルキラーT(NKT)細胞 / 抗原提示分子CD1d / 胸腺 / 分化 / 前駆細胞 / CD1d

Research Abstract

The presently held opinion, called "mainstream model of development", proposes that the NKT cells are developed after CD4, CD8-double-positive(DP) thymocytes. However, we have reported previously about identification of NKT cell precursors in the double-negative 4(DN4) stage of development that is before reaching DP stage, indicating NKT cells arise from earlier stage. Here, we characterized NKT precursor cells in DN4 stage by single cell sorting and qRT-PCR analysis, and also role of CD1d in the development of NKT cells by using NKT-cloned mice with CD1d-deficient background. Better understanding of developmental aspects of NKT cell lineage will hopefully lead to the development of more efficient clinical intervention methods to fight various immune-compromised diseases.

Research Products

• [Journal Article] Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant Valpha14-Jalpha 18 TCRalpha gene (2010)
  • Author(s): Watarai H, Rybochkin A, Hongo N, Nagata Y, Sakata S, Sekine E, Dashtsoodol N, Tashiro T, Fujii S, Shimizu K, Mori K, Masuda K, Kawamoto H, Koseki H, Taniguchi M.
  • Journal Title: Blood Volume: 115 Pages: 230-237
  • Peer Reviewed
• [Journal Article] The specialized iNKT cell system recognizes glycolipid antigens and bridges the innate and acquired immune systems with the potential applications for cancer therapy (2010)
  • Author(s): Taniguchi M, Tashiro T, Dashtsoodol N, Hongo N, Watarai H.
  • Journal Title: Int. Immunol Volume: 22 Pages: 1-6
  • NAID: 10027390882
  • Peer Reviewed
• [Journal Article] The specialized iNKT cell system recognizes glycolipid antigens and bridges the innate and acquired immune systems with potential applications for cancer therapy (2010)
  • Author(s): Taniguchi M., et al.
  • Journal Title: International Immunology 22 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant V{alpha}14-J{alpha}18 TCR{alpha} gene (2010)
  • Author(s): Watarai H., et al.
  • Journal Title: Blood 115 Pages: 230-237
  • Peer Reviewed
• [Presentation] 胸腺CD4 CD8両陰性中のNKT前駆細胞の分化にはIL-7受容体alpha鎖とSAP分子が必要である (2011)
  • Author(s): Dashtsoodol N, Ren Y, Taniguchi M
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-27
• [Presentation] Interleukin-7 receptor alpha(IL7Ra), SLAM-associated protein(SAP) and PLZF-dependent development of CD4, 8 double-negative thymocytes with NKT cell lineage potential (2011)
  • Author(s): Dashtsoodol N, Ren Y, Sekine-Kondo E, Watarai H, Taniguchi M.
  • Organizer: 6^<th> International Symposium on CD1 and NKT cells
  • Place of Presentation: Chicago, USA
  • Year and Date: 2011-09-25
• [Presentation] Interleukin-7 receptor alpha (IL7Ra), SLAM-associated protein (SAP) and PLZF-dependent development of CD4, 8 double-negative thymocytes with NKT eell lineage potential (2011)
  • Author(s): Nyambayar Dashtsoodol, Yue Ren, Etsiko Sekine-Kondo, Hiroshi Watarai, Masaru Taniguchi
  • Organizer: 6^<th> International Symposium on CD1 and NKT cells
  • Place of Presentation: Chicago, USA
  • Year and Date: 2011-09-25
• [Presentation] NKT Cell Development Revisited : An alternative developmental pathway of NKT cell from CD4, 8 double-negative precursors and it's developmental requirements (2011)
  • Author(s): Nyambayar Dashtsoodol
  • Organizer: IMSUT/RCAST-Chiba University Global COE Joint Retreat 2011
  • Place of Presentation: 大磯プリンスホテル(神奈川)
  • Year and Date: 2011-09-18
• [Presentation] Identification of NKT cell precursors in a subset of DN4 cells (2010)
  • Author(s): Dashtsoodol N, Kurimoto K, Watarai H, Saitou M, Taniguchi M.
  • Organizer: 14^<th> International Congress on Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-22
• [Presentation] Identification of NKT cell precursors in a subset of DN4 cells (2010)
  • Author(s): ニャムバヤル ダシツォードル
  • Organizer: 第14回国際免疫学会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-08-22
• [Presentation] Current Advances in Immunology, Microbiology and Allergology (2010)
  • Author(s): Dashtsoodol N, Taniguchi M
  • Organizer: Identification of CD4, CD8 DN precursors of the NKT cell lineage. Second International
  • Place of Presentation: Ulaanbaatar, Mongolia
  • Year and Date: 2010-06-24
• [Presentation] Identification of CD4, CD8 DN precursors of the NKT cell lineage (2010)
  • Author(s): ニャムバヤル ダシツォードル
  • Organizer: Second International Conference "Current Advances in Immunology, Microbiology and Allergology"
  • Place of Presentation: ウランバートル市、モンゴル国立保健大学
  • Year and Date: 2010-06-24
• [Book] Mechanisms of NKT-cell-mediated adjuvant activity and function of iPS-derived NKT cells. Natural Killer T cells : Balancing the Regulation of Tumor Immunity (2011)
  • Author(s): Taniguchi M, Fujii S, Nakayama T, Motohashi S, Dashtsoodol N, Watarai H, Harada M
  • Publisher: Springer
• [Book] Natural Killer T cells : Balancing the Regulation of Tumor Immunity NKT-cell-mediated adjuvant activity and function of iPS-derived NKT cells (2011)
  • Author(s): Taniguchi M, Fujii S, Nakayama T, Motohashi S, Dashtsoodol N, Watarai H, Harada M
  • Publisher: Springer
• [Remarks]
  • URL: http://www.riken.jp/r-world/research/lab/rcai/regulation/index.html
• [Remarks]
  • URL: http://web.rcai.riken.jp/en/labo/regulation/
• [Remarks]
  • URL: http://www.riken.jp/r-world/research/lab/rcai/regulation/index.html
• [Remarks]
  • URL: http://web.rcai.riken.jp/en/labo/regulation