Development of the new immuno-suppresant based on the regulation of lipid rafts.

• Project/Area Number: 19390276
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kanazawa Medical University
• Principal Investigator: UMEHARA Hisanori Kanazawa Medical University, 医学部, 教授 (70247881)
• Co-Investigator(Kenkyū-buntansha): OKAZAKI Toshirou 鳥取大学, 医学部, 教授 (40233308) ; TANAKA Masao 金沢医科大学, 医学部, 准教授 (10332719) ; MASAKI Yasufumi 金沢医科大学, 医学部, 准教授 (40238895) ; FUKUSHIMA Toshihiro 金沢医科大学, 医学部, 准教授 (60251998) ; JIN Zhe-xiong 金沢医科大学, 医学部, 助教 (90345570)
• Co-Investigator(Renkei-kenkyūsha): KAWANAMI Takafumi 金沢医科大学, 医学部, 助教 (20350762) ; SAWAKI Toshioki 金沢医科大学, 医学部, 助教 (90534694)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2008: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000); Fiscal Year 2007: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: 膠原病学 / スフィンゴミエリン / リピッドラフト / T細胞レセプター / LAT / ZAP-70 / シグナル伝達

Research Abstract

T細胞活性化に重要なリピッドラフトについて細胞膜スフィンゴミエリンに着目して解析した.スフィンゴミエリン欠質T細胞では,有意にT細胞レセプター刺戟による細胞活性化およびそのシグナル伝達が低下していた.全身性エリテマトーデス患者ではT細胞上のリピッドラフト発現が有意に亢進しており,リピッドラフト制御による新たな免疫抑制剤が治療に有効である可能性が明らかになった.

Research Products

• [Journal Article] Impaired TCR signalingthrough dysfunction of lipid rafts sphingomyelin synthese 1 (SMS1)-nock down T cells Int. (2008)
  • Author(s): Jin, Z.-X., C.-R. Huang, S. Goda, L. Dong, T. Kawanami, T. Sawaki, T. Sakai, X.-P. Tong, Y. Masaki, T. Fukushima, M. Tanaka, T. Mimori, H. Tojo, E. T. Bloom, T. Okazaki, and H. Umehara
  • Journal Title: Immunology 20 Pages: 1427-1437
  • Peer Reviewed
• [Journal Article] Successful treatment of amegakaryocytic thrombocytopenia with tuximab in a patient with systemic lupus erythematosus. (2008)
  • Author(s): Fukushima, T., L. Dong, T. Sakai, T. Sawaki, M. Tanaka, Y. Masaki, M. Kuwana, Y. Hirose, and H. Umehara.
  • Journal Title: Lupus 17 Pages: 210-214
  • Peer Reviewed
• [Journal Article] Proposal for a new clinical entity, IgG4-positive multi-organ lymphoproliferative syndrome (IgG4+MOLPS): Analysis of 64 cases of IgG4-related isorders including Mikulicz's disease and autoimmune pancreatitis. (2008)
  • Author(s): Masaki, Y., L. Dong, N. Kurose, K. Kitagawa, Y. Morikawa, M. Yamamoto, H. Takahashi, Y. Shinomura, K. Imai, T. Saeki, A. Azumi, S. Nakata, E. Sugiyama, S. Matsui, T. Origuchi, S. Nishiyama, I. Nishimori, T. Nojima, K. Yamada, M. Kawano, Y. Zen, M. Kaneko, K. Miyazaki, K. Tsubota, K. Tomoda, T. Sawaki, T. Kawanami, M. Tanaka, T. Fukushima, S. Sugai, and H. Umehara.
  • Journal Title: Ann. Rheum. Dis.
  • Peer Reviewed
• [Journal Article] Impaired TCR signaling through dysfunction of lipid rafts in sphingomye lin synthase 1 (SMS1)-knockdown T cells. (2008)
  • Author(s): Jin ZX
  • Journal Title: Int. Immun 20 Pages: 1427-1437
  • Peer Reviewed
• [Journal Article] Successful treatment of amegakaryocytic thrombocytopenia with anti-CD20 antibody (rituximab)in a patients with systemic lupus erythematosus. (2008)
  • Author(s): Fukushima T
  • Journal Title: Lupus. 17 Pages: 210-214
  • Peer Reviewed
• [Journal Article] Proposal for a new clinical entity, IgG4-positive multi-organ lymphoproli ferative syndrome : Analysis of 64 cases of IgG4-related disorders. (2008)
  • Author(s): Masaki Y
  • Journal Title: Arm Rheum Dis. 13(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Clonality analysis of lymphoproliferative disorders in lymphocytes infiltration from patients with Sjogren's syndrome (SS) (2007)
  • Author(s): Dong, L., Y. Masaki, T. Takegami, Z.-X. Jin, C.-R. Huang, T. Fukushima, T. Sawaki, T. Kawanami, T. Saeki, K. Kitagawa, S. Sugai, T. Okazaki, Y. Hirose, and H. Umehara.
  • Journal Title: Clin. Exp. Immunol. 150 Pages: 279-284
  • Peer Reviewed
• [Journal Article] Cloning and expression of two human recombinant monoclonal Fab fragments specific for EBV viral capsid antigen. (2007)
  • Author(s): Dong, L., Y. Masaki, T. Takegami, T. Kawanami, I. Kunihiko, Z.-X. Jin, C.-R. Huang, X.-P. Tong, T. Fukushima, M. Tanaka, T. Sawaki, T. Sakai, S. Sugai, T. Okazaki, Y. Hirose, and H. Umehara.
  • Journal Title: Int. Immunol. 19 Pages: 331-336
  • NAID: 10020111440
  • Peer Reviewed
• [Journal Article] Sjogren's syndrome and lymphoma development. (2007)
  • Author(s): Dong, L., Y. Masaki, M. Tanaka, T. Fukushima, T. Okazaki, and H. Umehara.
  • Journal Title: Clin. Immunol. Rev. 3 Pages: 289-296
  • Peer Reviewed
• [Journal Article] Efficacy and Safety of Mizoribine for the Treatment of Sjogren's syndrome : A Multicenter Open-label Clinical Trial. (2007)
  • Author(s): Nakayamada, S., K. Saito, H. Umehara, N. Ogawa, T. Sumida, S. Ito, S. Minota, H. Nara, H. Kondo, J. Okada, T. Mimori, H. Yoshifuji, H. Sano, N. Hashimoto, S. Sugai, and Y. Tanaka.
  • Journal Title: Mod. Rheumatol. 17 Pages: 464-469
  • NAID: 10020178053
  • Peer Reviewed
• [Journal Article] Clonality analysis of lymphoproliferative disorders in lymphocytes infiltration from patients with Sjogren's syndrome(SS). (2007)
  • Author(s): Dong, L.,
  • Journal Title: Clin. Exp. Immunol. 150 Pages: 279-284
  • Peer Reviewed
• [Journal Article] Cloning and expression of two human recombinant monoclonal Fab fragments specific for EBV viral capsid antigen. (2007)
  • Author(s): Dong, L.,
  • Journal Title: Int. Immunol. 19
  • Peer Reviewed
• [Journal Article] Sjogren's syndrome and lymphoma development.(Review) (2007)
  • Author(s): Dong, L.,
  • Journal Title: Clin. Immunol. Rev. 3 Pages: 289-296
  • Peer Reviewed
• [Journal Article] Efficacy and Safety of Mizoribine for the Treatment of Sjogren's Syndrome. A Multicenter Open-label Clinical Trial. (2007)
  • Author(s): Nakayamada, S.
  • Journal Title: Mod. Rheum. 17 Pages: 464-469
  • Peer Reviewed