Genetic reconstitution of autoimmune diseases in mice.

• Project/Area Number: 19689012
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: The University of Tokushima
• Principal Investigator: OKAZAKI Taku 徳島大学, 疾患ゲノム研究センター, 教授 (00362468)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000); Fiscal Year 2009: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2007: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
• Keywords: 遺伝子 / 細胞 / 実験動物 / 自己免疫疾患 / 連鎖解析 / I型糖尿病 / 免疫学 / ゲノム / 自己免疫寛容 / 末梢神経炎 / 多遺伝子疾患

Outline of Final Research Achievements

We have identified several autoimmune susceptible loci by genetic linkage analyses on animal models of type I diabetes, peripheral neuropathy, and myocarditis. We have also succeeded in reconstituting type I diabetes on the disease-resistant strain by introducing diabetes susceptible loci.

Research Products

• [Journal Article] PD-1-mediated suppression of IL-2 production induces CD8+ T-cell anerav in vivo (2009)
  • Author(s): Chikuma S, et.al.
  • Journal Title: J. Immunol. (印刷中)
  • Peer Reviewed
• [Journal Article] Identification of QTLs that modify peripheral neuropathy in NOD. H2^b-Pdcdl mice (2009)
  • Author(s): Jiang F, et.al.
  • Journal Title: Int. Immunol. (印刷中)
  • Peer Reviewed
• [Journal Article] T cell suppression by programmed cell death 1 ligand 1 on retinal pigment epithelium during inflammatory conditions (2009)
  • Author(s): Sugita S, et.al.
  • Journal Title: Invest Ophthalmol Vis Sci. (印刷中)
  • Peer Reviewed
• [Journal Article] Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling (2009)
  • Author(s): Kido M, et.al.
  • Journal Title: Gastroenterology 135 Pages: 1333-43
  • Peer Reviewed
• [Journal Article] PD-1 deficiency reveals various tissue-specific autoimmunity by H-2b and dose-dependent requirement of H-2g7 for diabetes in NOD mice (2008)
  • Author(s): Yoshida T, et.al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 3533-8
  • Peer Reviewed
• [Journal Article] The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors (2008)
  • Author(s): Lin DY, et.al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 3011-6
  • Peer Reviewed
• [Journal Article] The programmed death-1 and interleukin-10 pathways play a down-modulatory role in LP-BM 5 retrovirus-induced murine immunodeficiency syndrome (2008)
  • Author(s): Green KA, et.al.
  • Journal Title: J. Virol. 82 Pages: 2456-69
  • Peer Reviewed
• [Journal Article] Specific and high-affinity binding of tetramerized PD-L 1 extracellular domain to PD-1-expressing cells : possible application to enhance T cell function (2007)
  • Author(s): Terawaki S, et.al.
  • Journal Title: Int. Immunol. 19 Pages: 881-90
  • Peer Reviewed
• [Journal Article] PD-1 and PD-1 ligands : from discovery to clinical application (2007)
  • Author(s): Okazaki T and Honjo T
  • Journal Title: Int. Immunol. 19 Pages: 813-24
  • NAID: 10020108933
  • Peer Reviewed
• [Presentation] Genetic dissection and reconstitution of autoimmune diseases using PD-1 deficient mice (2008)
  • Author(s): Okazaki T and Honjo T
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2008-12-10
• [Presentation] Transcriptional mechanisms of mouse PD-1 gene (2008)
  • Author(s): Terawaki S, et.al.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2008-12-03
• [Presentation] PD-1 induces T cell anergy by limiting autonomous IL-2 production (2008)
  • Author(s): Chikuma S, et.al.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2008-12-03
• [Presentation] Involvement of IFN-g producing CD 4+PD-1+T cells in lupus-prone NZB/W F1 mice (2008)
  • Author(s): Kasagi S, et.al.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2008-12-03
• [Presentation] The PD-1 : PD-L1 pathway inhibits the protective immunity and contributes to the bacterial persistence in mycobacterial infection (2008)
  • Author(s): Sakai S, et.al.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2008-12-02
• [Presentation] Roles of programmed death-1 (PD-1)/PD-1 ligands pathway in the development of murine experimental autoimmune uveoretinitis (EAU) (2008)
  • Author(s): Usui Y, et.al.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2008-12-01
• [Presentation] Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signalin (2008)
  • Author(s): Kido M, et.al.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2008-12-01
• [Presentation] Expression of PD-1/PD-L 1 in the development of lupus-like nephrit is in NZB/W mice (2007)
  • Author(s): Shinpei Kasagi, et.al.
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 東京都
  • Year and Date: 2007-11-20
• [Presentation] 抗トロポニンI抗体と拡張型心筋症 (2007)
  • Author(s): 岡崎拓、本庶佑
  • Organizer: 第28回日本アフェレーシス学会
  • Place of Presentation: 久留米市
  • Year and Date: 2007-11-17
• [Presentation] Genetic dissection of autoimmunity using PD-1 deficient mice (2007)
  • Author(s): Taku Okazaki
  • Organizer: COE International Symposium 2007
  • Place of Presentation: 京都市
  • Year and Date: 2007-06-02