Roles of PD-1 and AIDA in inflammation-induced tumorigenesis.

• Project/Area Number: 21790473
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: The University of Tokushima
• Principal Investigator: OKAZAKI Il-mi The University of Tokushima, 疾患ゲノム研究センター, 助教 (50452339)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 遺伝子 / 細胞 / 実験動物 / 炎症 / 発がん / 免疫学 / がん / 自己免疫疾患 / 突然変異

Research Abstract

The incidence of colon cancer in mice deficient for IL-10 was not increased by PD-1 deficiency. We have found that PD-1 and AIDA (LAG-3) additively suppressed the activation of T cells upon antigen stimulation. We have analyzed mice deficient for both PD-1 and AIDA (LAG-3) and found that regulatory T cells retained the regulatory function and T cells were biased toward Thl in these mice.

Research Products

• [Journal Article] Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation. (2011)
  • Author(s): Okazaki IM, Okawa K, Kobayashi M, Yoshikawa K, Kawamoto S, Nagaoka H, Shinkura R, Kitawaki Y, Taniguchi H, Natsume T, Iemura S, Honjo T.
  • Journal Title: Proc Natl Acad Sci U S A. 108(19) Pages: 7920-7925
  • Peer Reviewed
• [Journal Article] PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice. (2011)
  • Author(s): Okazaki T, Okazaki IM, Wang J, Sugiura D, Nakaki F, Yoshida T, Kato Y, Fagarasan S, Muramatsu M, Eto T, Hioki K, Honjo T.
  • Journal Title: J Exp Med. 208(2) Pages: 395-407
  • Peer Reviewed
• [Journal Article] PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice. (2011)
  • Author(s): Okazaki T, et al.
  • Journal Title: J.Exp.Med. Volume: 208 Pages: 395-407
  • Peer Reviewed
• [Journal Article] PD-1 deficiency results in the development of fatal myocarditis in MRL mice. (2010)
  • Author(s): Wang J, Okazaki IM, Yoshida T, Chikuma S, Kato Y, Nakaki F, Hiai H, Honjo T, Okazaki T.
  • Journal Title: Int.Immunol. 22(6) Pages: 443-452
  • Peer Reviewed
• [Journal Article] AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination. (2009)
  • Author(s): Kobayashi M, Aida M, Nagaoka H, Begum NA, Kitawaki Y, Nakata M, Stanlie A, Doi T, Kato L, Okazaki IM, Shinkura R, Muramatsu M, Kinoshita K, Honjo T.
  • Journal Title: Proc Natl Acad Sci U S A. 106(52) Pages: 22375-22380
  • Peer Reviewed
• [Journal Article] Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes. (2009)
  • Author(s): Sabouri Z, Okazaki IM, Shinkura R, Begum N, Nagaoka H, Tsuchimoto D, Nakabeppu Y, Honjo T.
  • Journal Title: Int Immunol. 21(8) Pages: 947-955
  • Peer Reviewed
• [Presentation] a newly established animal model of autoimmunity. (2010)
  • Author(s): Okazaki T, Okazaki IM, Sugiura D.Aida
  • Organizer: 2010年日本免疫学会シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-04
• [Presentation] Aida, a newly established animal model of autoimmunity. (2010)
  • Author(s): Okazaki T, et al.
  • Organizer: 2010年日本免疫学会シンポジウム
  • Place of Presentation: 一橋記念講堂(東京都)
  • Year and Date: 2010-12-03
• [Presentation] Identification of the causal gene of aida mouse, a newly established animal model of autoimmunity. (2010)
  • Author(s): Okazaki T, Sugiura D, Okazaki IM, Honjo T.
  • Organizer: The 14th International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-27
• [Presentation] Identification of the causal gene of aida mouse, a newly established animal model of autoimmunity. (2010)
  • Author(s): Okazaki T, et al.
  • Organizer: The 14th International Congress of Immunology
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-08-27
• [Presentation] Identification of QTLs that modify peripheral neuropathy in NOD.H2b-PD-1KO mice. (2010)
  • Author(s): Okazaki IM, Jiang F, Honjo T, Okazaki T.
  • Organizer: The 14th International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-23
• [Presentation] Identification of QTLs that modify peripheral neuropathy in NOD.H2b-PD-1KO mice. (2010)
  • Author(s): Okazaki IM, et al.
  • Organizer: The 14th International Congress of Immunology
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-08-23
• [Presentation] Requirement of isotype-switched and somatically mutated autoantibodies for the development of autoimmune diseases in BALB/c-PD-1KO mice. (2010)
  • Author(s): Okazaki T, et al.
  • Organizer: The 4th International Conference on B cells and Autoimmunity
  • Place of Presentation: 奈良ロイヤルホテル(奈良県)
  • Year and Date: 2010-08-20
• [Presentation] Requirement of isotype-switched and somatically mutated autoantibodies for the development of autoimmune diseases in BALB/c-PD-1KO mice. (2010)
  • Author(s): Okazaki T, Sugiura D, Okazaki IM, Honjo T.
  • Organizer: The 4th International Conference on B cells and Autoimmunity
  • Place of Presentation: 奈良
  • Year and Date: 2010-08-19
• [Presentation] PD-1 deficiency results in the development of fatal myocarditis in MRL mice. (2010)
  • Author(s): 岡崎拓、岡崎一美
  • Organizer: 第9回四国免疫フォーラム
  • Place of Presentation: 松山
  • Year and Date: 2010-06-19
• [Presentation] PD-1 deficiency results in the development of fatal myocarditis in MRL mice. (2010)
  • Author(s): 岡崎拓, 他
  • Organizer: 第9回四国免疫フォーラム
  • Place of Presentation: 愛媛大学(愛媛県)
  • Year and Date: 2010-06-19
• [Presentation] 自己免疫性胃炎モデルマウスにお ける自己抗原同定の試み (2009)
  • Author(s): 梶原武雄, 杉浦大祐, 岡崎一美, 岡崎拓
  • Organizer: 第33回徳島県医学検査学会
  • Place of Presentation: 徳島
  • Year and Date: 2009-12-13
• [Presentation] Involvement of Topoisomerase I in class switch recombination. (2009)
  • Author(s): Kobayashi M, Aida M, Nagaoka H, Begum NA, Kitawaki Y, Nakata M, Stanlie A, Doi T, Kato L, Okazaki IM, Shinkura R, Muramatsu M, Kinoshita K, Honjo T.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] Involvement of Topoisomerase I in class switch recombination of Immunoglobulin genes. (2009)
  • Author(s): Kobayashi M, Aida M, Doi T, Nagaoka H, Kitawaki Y, Nakata M, Kato L, Stanlie A, Begum NA, Okazaki IM, Shinkura R, Muramatsu M, Kinoshita K, Honjo T.
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Remarks] ホームページ等
  • URL: http://www.genome.tokushima-u.ac.jp/dir/