Mechanisms of tolerance induction by apoptotic cell phagocytosis

• Project/Area Number: 19390117
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: TANAKA Masato The Institute of Physical and Chemical Research, 自然免疫研究チーム, チームリーダー (00294059)
• Co-Investigator(Kenkyū-buntansha): KIKUCHI Kazuhiro 独立行政法人理化学研究所, 自然免疫研究チーム, 研究員 (90391929) ; 三宅 靖廷 独立行政法人理化学研究所, 自然免疫研究チーム, 研究員 (10392143)
• Co-Investigator(Renkei-kenkyūsha): MIYAKE Yasunobu 独立行政法人理化学研究所, 自然免疫研究チーム, 研究員 (10392143)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2009: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2008: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2007: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 死細胞 / 貪食 / 食細胞 / マクロファージ / 樹状細胞 / 免疫寛容 / 辺縁帯 / 細胞死 / 抗原提示 / 脾臓 / 自己免疫疾患

Research Abstract

The intravenous injection of apoptotic cells can induce cell associated antigen-specific immunosuppression or tolerance. This mechanism of tolerance induction requires the contributions of two populations of cells in the splenic marginal zone, macrophages that rapidly clear corpse in the blood flow, and CD8・^+, CD103^+ DCs that selectively phagocytose dead cell and subsequently present dead cell-associated antigen.

Research Products

• [Journal Article] xCT deficiency accelerates chemically induced tumorigenesis (2010)
  • Author(s): Nabeyama, A., Y. Miyake, (12人中4番目) M. Tanaka(12人中12番目)
  • Journal Title: Proc Natl Acad Sci USA 107 Pages: 6436-6441
  • Peer Reviewed
• [Journal Article] Time-lapse observation of cellular function with fluorescent probe reveals novel CTL-target cell interactions. (2009)
  • Author(s): Tomura, M., M. Tanaka
  • Journal Title: Int Immunol 21 Pages: 1145-50
  • NAID: 10027389771
  • Peer Reviewed
• [Journal Article] 食細胞による死細胞貪食を介した免疫寛容誘導 (2009)
  • Author(s): 三宅靖延、田中正人
  • Journal Title: 医学のあゆみ 230 Pages: 640-645
• [Journal Article] Tanaka, Novel subset of CD8{alpha}+ dendritic cells localized in the marginal zone is responsible for tolerance to cell-associated antigens. (2009)
  • Author(s): Qiu, C.H., Y. Miyake, H. Kaise, H. Kitamura, O. Ohara, M. Tanaka
  • Journal Title: J. Immunol 182 Pages: 127-4136
  • Peer Reviewed
• [Journal Article] Time-lapse observation of cellular function with fluorescent probe reveals novel CTL-target cell interactions (2009)
  • Author(s): Tomura, M, 他
  • Journal Title: International Immunology 21 Pages: 1145-1150
  • Peer Reviewed
• [Journal Article] Novel subset of CD8{alpha}+dendritic cells localized in the marginal zone is responsible for tolerance to cell-associated antigens (2009)
  • Author(s): Qiu, C.H., 他
  • Journal Title: Journal of Immunology 182 Pages: 4127-4136
  • Peer Reviewed
• [Journal Article] 食細胞による死細胞食食を介した免疫寛容誘導 (2009)
  • Author(s): 三宅靖延, 他
  • Journal Title: 医学のあゆみ 230 Pages: 640-645
• [Journal Article] Maintenance of self-tolerance by apoptotic cell clearance. (2008)
  • Author(s): Tanaka, M., Miyake, Y., Asano, K.
  • Journal Title: Front Biosci 13 Pages: 6043-6049
  • Peer Reviewed
• [Journal Article] 死細胞の貪食異常と自己免疫疾患 (2008)
  • Author(s): 浅野謙一、田中正人
  • Journal Title: 実験医学 26 Pages: 3019-3024
• [Journal Article] 細胞に含有される抗原に対する免疫寛容誘導と辺縁帯マクロファージ (2008)
  • Author(s): 三宅靖延、田中正人
  • Journal Title: 臨床免疫・アレルギー科 50 Pages: 345-349
  • NAID: 40016259732
• [Journal Article] Maintenance of self-tolerance by apoptotic cell clearance (2008)
  • Author(s): MasatoTanaka, 他
  • Journal Title: Frontiers in Bioscience 13 Pages: 6043-6049
  • Peer Reviewed
• [Journal Article] Critical role of macrophages in the marginal zone in the suppression of immune responses to apoptotic cell-associated antigens (2007)
  • Author(s): Miyake, Y., Asano, K., Tanaka, M., (6人中6番目)
  • Journal Title: J Clin Invest. 117 Pages: 2268-2278
  • Peer Reviewed
• [Journal Article] Protective role of macrophages in noninflammatory lung injury caused by selective ablation of alveolar epithelial type II cells (2007)
  • Author(s): Miyake, Y., Tanaka, M., (6人中6番目)
  • Journal Title: J. Immunol 178 Pages: 5001-5009
  • Peer Reviewed
• [Journal Article] Bridge over troubled water: milk fat globule epidermal growth factor 8 promotes human monocyte-derived macrophage clearance of non-blebbing phosphatidylserine-positive target cells. (2007)
  • Author(s): Witasp, E., Tanaka, M., (8人中5番目)
  • Journal Title: Cell Death and Differentiation 14 Pages: 1063-1065
  • Peer Reviewed
• [Journal Article] Apoptotic Cell Clearance and Autoimmune Disorder. (2007)
  • Author(s): Tanaka, M., Miyake, Y.
  • Journal Title: Current Medicinal Chemistry 14 Pages: 2892-2897
  • Peer Reviewed
• [Journal Article] Construction of an open-access database that integrates cross-reference information from the transcriptome and proteome of immune cells. (2007)
  • Author(s): Hijikata, A., Tanaka, M., (39名中32番目)
  • Journal Title: Bioinformatics 23 Pages: 2934-2941
  • Peer Reviewed
• [Journal Article] Apoptotic Cell Clearance and Autoimmune Disorder. (2007)
  • Author(s): Tanaka, M.
  • Journal Title: Current Medicinal Chemistry 14 Pages: 2892-2897
  • Peer Reviewed
• [Journal Article] Critical role of macrophages in the marginal zone in the suppression of immune responses to apoptotic cell-associated antigens. (2007)
  • Author(s): Miyake, Y.
  • Journal Title: The Journal of Clinical Investigation 117 Pages: 2268-2278
  • Peer Reviewed
• [Journal Article] Protective role of macrophages in noninflammatory lung injurycaused by selective ablation of alveolar epithehal type II cells. (2007)
  • Author(s): Miyake, Y.
  • Journal Title: The Journal of Immunology 178 Pages: 5001-5009
  • Peer Reviewed
• [Journal Article] Bridge over troubled water:milk fat globule epidermal growth factor 8 promotes human monocyte-derived macrophage clearanceof non-blebl)ing phosphatidylserine-positive target cells. (2007)
  • Author(s): Witasp, E.
  • Journal Title: Cell Death and Differentiation 14 Pages: 1063-1065
  • Peer Reviewed
• [Journal Article] Construction of an open-access database that integratescross-reference information from the transcriptome and proteomeof immune cells. (2007)
  • Author(s): Hijikata, A.
  • Journal Title: Bioinformatics 23 Pages: 2934-2941
  • Peer Reviewed
• [Journal Article] Novel Subset of CD8α^+Dendritic Cells localized in the Marginal Zone is Responsible for Tolerance to Cell-Associated Antigens
  • Author(s): Chun-Hong Qiu, 他
  • Journal Title: Journal of Immunology
  • Peer Reviewed
• [Presentation] 死細胞貪食による免疫制御機構 (2010)
  • Author(s): 田中正人
  • Organizer: 第9回細胞死研究会
  • Place of Presentation: 京都
  • Year and Date: 2010-01-18
• [Presentation] Strategy of tolerance induction by apoptotic cell clearance (2009)
  • Author(s): Masato Tanaka
  • Organizer: 2009 4th Medical Biotech Forum
  • Place of Presentation: Dalian, China
  • Year and Date: 2009-08-10
• [Presentation] 死細胞付随抗原に対する免疫寛容誘導現象を用いた自己免疫疾患の抑制 (2009)
  • Author(s): 田中正人
  • Organizer: 第5回自己免疫疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-11
• [Presentation] Mechanism of tolerance induction to cell-associated antigens by apoptotic cell clearance (2009)
  • Author(s): Tanaka M.
  • Organizer: Gordon Research Conferences, Apoptotic Cell Recognition & Clearance
  • Place of Presentation: New London, USA
  • Year and Date: 2009-06-29
• [Presentation] Mechanism of tolerance induction to cell-associated antigens by apoptotic cell clearance, Gordon Research Conferences (2009)
  • Author(s): Masato Tanaka
  • Organizer: Apoptotic Cell Recognition & Clearance
  • Place of Presentation: New London, USA
• [Presentation] Apoptotic cell clearance and self-tolerance (2008)
  • Author(s): 田中正人
  • Organizer: 第15回武田科学振興財団生命科学シンポジウム
  • Place of Presentation: シェラトン都ホテル東京(目黒)
  • Year and Date: 2008-12-03
• [Presentation] 死細胞貪食による免疫寛容誘導機構 (2008)
  • Author(s): 田中正人
  • Organizer: 第29回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-09
• [Presentation] 死細胞貪食による免疫寛容誘導機構 (2008)
  • Author(s): 田中正人
  • Organizer: 第29回日本炎症・再生医学会
  • Place of Presentation: 都市センターホテル(麹町)
  • Year and Date: 2008-07-09
• [Presentation] Apoptotic cell clearance and self-tolerance (2008)
  • Author(s): 田中正人
  • Organizer: 第15回武田科学振興財団生命科学シンポジウム
  • Place of Presentation: 東京
• [Presentation] Mechanisms of tolerance induction to cell-associated antigens (2007)
  • Author(s): 田中正人
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Presentation] Mechanisms of tolerance induction to cell-associated antigens (2007)
  • Author(s): Tanaka, M.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: Shjhagawa,Japan
  • Year and Date: 2007-11-20
• [Presentation] Tolerance induction by apoptotic cell clearance, RCAI-JSI International Symposimu on Immunology 2007 (2007)
  • Author(s): Masato Tanaka
  • Organizer: Development and Maintenance of Immune System
  • Place of Presentation: Yokohama
  • Year and Date: 2007-07-27
• [Presentation] Tolerance induction by apoptotic cell clearance. (2007)
  • Author(s): Tanaka, M.
  • Organizer: RCAI-JSI Intemational Symposium on Immunology 2007:Development and Maintenance of Immune System
  • Place of Presentation: Yokohama,Japan
  • Year and Date: 2007-07-27
• [Presentation] Mechanisms of tolerance induction to cell-associated antigens (2007)
  • Author(s): Masato Tanaka
  • Organizer: Joint Meeting RIKEN-MPG "Activation and Regulation of the Immune System"
  • Place of Presentation: Germany
  • Year and Date: 2007-04-17
• [Presentation] Mechanisms of tolerance induction to cell-associated antigens. (2007)
  • Author(s): Tanaka, M.
  • Organizer: Joint Meeting RIKEN-MPG:Activation and Regulation of the Immune System
  • Place of Presentation: Berlim,Germany
  • Year and Date: 2007-04-16
• [Presentation] Regulation of tolerance to cell-associated antigen by macrophages in the marginal zone (2007)
  • Author(s): Yasunobu Miyake
  • Organizer: Keystone symposia
  • Place of Presentation: Colorado, USA
  • Year and Date: 2007-04-11
• [Presentation] Macrophages in the marginal zone regulate selective clearance of dying cells by cd8alpha dendritic cells and induction of tolerance to cell-associated antigens (2007)
  • Author(s): Yasunobu Miyake
  • Organizer: The 20th Naito conference
  • Place of Presentation: Zushi
• [Presentation] Regulation of tolerance to cell-associated antigens by macrophages in the marginal zone. (2007)
  • Author(s): Miyake, Y.
  • Organizer: Keystone Symposia on Molecular and Cellular Biology:The Macrophage:Homeostasis, Immunoregulation and Diseases
  • Place of Presentation: Colorado,PSA
• [Presentation] Macrophages in the marginal zone regulate selective clearance of dying cells by CD8α dendritic cells and induction of tolerance to cell-associated antigens. (2007)
  • Author(s): Miyake, Y.
  • Organizer: 第20回内藤コンファレンス「自然免疫の医学・生物学[III]」
  • Place of Presentation: Zushi,Japan
• [Remarks]
  • URL: http://web.rcai.riken.jp/en/labo/innate/