Immunological disorder via Toll like receptors expressed by sex chromosome in systemic lupus erythematosus

• Project/Area Number: 21591272
• Research Category: Grant-in-Aid for Scientific Research (C)
• 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: Juntendo University
• Principal Investigator: AMANO Hirofumi 順天堂大学, 医学部, 准教授 (50318474)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Toll / 様受容体 / 全身性エリテマトーデス / Toll様受容体 / BXSBマウス / Yaa遺伝子 / Fc_Yレセプター / B細胞

Research Abstract

Yaa(Y-linked autoimmune acceleration) mutation, which develop autoimmune diseases in lupus-prone BXSB mice turned out to be a translocation of X chromosomal telomeric region containing tlr7 gene onto Y chromosome. Meanwhile, Fc_YRIIB is known as a negative regulator of B cell activation. We introduced the Yaa mutation to the Fc_YRIIB knockout mice which develop rheumatoid arthritis. The Fc_YRIIB-/-. Yaa mice develop lupus like nephritis and we confirm the TLR7 duplication affect the specificity of disease phenotype in autoimmune background.

Research Products

• [Journal Article] Elevated serum level of circulating syndecan-1(CD138) in active systemic lupus erythematosus (2011)
  • Author(s): Minowa K, Amano H, Nakano S, Ando S, Watanabe T, Nakiri Y, Amano E, Tokano Y, Morimoto S, Takasaki Y.
  • Journal Title: Autoimmunity Volume: 44(5) Pages: 357-62
  • Peer Reviewed
• [Journal Article] SLEの病態と自然免疫-Toll-like receptorを中心に (2011)
  • Author(s): 天野浩文
  • Journal Title: リウマチ科 Volume: 46(2) Pages: 117-22
• [Journal Article] Fcγレセプターと全身性自己免疫疾患 (2011)
  • Author(s): 天野浩文
  • Journal Title: 日本臨床免疫学会会誌 Volume: 34(1) Pages: 1-7
  • NAID: 10029431513
• [Journal Article] Elevated serum level of circulating syndecan-1 (CD138) in active systemic lupus erythematosus (2011)
  • Author(s): Minowa K, et al
  • Journal Title: Autoimmunity Volume: 44 Pages: 357-362
  • Peer Reviewed
• [Journal Article] Single-center, retrospective analysis of efficacy and safety of tacrolimus as a second-line DMARD in combination therapy and the risk factors contributing to adverse events in 115 patients with rheumatoid arthritis (2011)
  • Author(s): Ogasawara, et al
  • Journal Title: Clin Rheumatol Volume: 31 Pages: 251-257
  • Peer Reviewed
• [Journal Article] Inhibitory IgG Fc receptor promoter region polymorphism is a key genetic element for murine systemic lupus erythematosus (2010)
  • Author(s): Lin Q, Hou R, Sato A, Ohtsuji M, Ohtsuji N, Nishikawa K, Tsurui H, Amano H, Amano E, Sudo K, Nishimura H, Shirai T, Hirose S.
  • Journal Title: Autoimmunity Volume: 34(4) Pages: 356-63
  • Peer Reviewed
• [Journal Article] The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population (2010)
  • Author(s): Shimane K, Kochi Y, Horita T, Ikari K, Amano H, Hirakata M, Okamoto A, Yamada R, Myouzen K, Suzuki A, Kubo M, Atsumi T, Koike T, Takasaki Y, Momohara S, Yamanaka H, Nakamura Y, Yamamoto K.
  • Journal Title: Arthritis Rheum Volume: 62(2) Pages: 574-9
  • Peer Reviewed
• [Journal Article] FTY720 exerts a survival advantage through the prevention of end-stage glomerular inflammation in lupus-prone BXSB mice (2010)
  • Author(s): Ando S, Amano H, Amano E, Minowa K, Watanabe T, Nakano S, Nakiri Y, Morimoto S, Tokano Y, Lin Q, Hou R, Ohtsuji M, Tsurui H, Hirose S, Takasaki Y.
  • Journal Title: Biochem Biophys Res Commun Volume: 394(3) Pages: 804-10
  • Peer Reviewed
• [Journal Article] Up-regulation of the endoplasmic reticulum transmembrane protein UNC93B in the B cells of patients with active systemic lupus erythematosus (2010)
  • Author(s): Nakano S, Morimoto S, Suzuki S, Watanabe T, Amano H, Takasaki Y.
  • Journal Title: Rheumatology(Oxford) Volume: 49(5) Pages: 876-81
  • Peer Reviewed
• [Journal Article] Evidence that Yaa-induced loss of marginal zone B cells is a result of dendritic cell-mediated enhanced activation (2010)
  • Author(s): Santiago-Raber ML, Amano H, Amano E, Fossati-Jimack L, Swee LK, Rolink A, Izui S.
  • Journal Title: J Autoimmun Volume: 34(4) Pages: 349-55
  • Peer Reviewed
• [Journal Article] The long-term prognosis of lupus nephritis patients treated with intravenous cyclophosphamide (2010)
  • Author(s): Matsuyama N, Morimoto S, Tokano Y, Amano H, Nozawa K, Isonuma H, Hashimoto H, Takasaki Y.
  • Journal Title: Intern Med Volume: 49(9) Pages: 823-8
  • NAID: 130000251879
  • Peer Reviewed
• [Journal Article] SLEの疾患活動性の評価法と問題点-SLEDAI(original, SLEDAI-2K)とBILAG(classicと2004など) (2010)
  • Author(s): 天野浩文
  • Journal Title: リウマチ科 Volume: 43(6) Pages: 585-592
• [Journal Article] Inhibitory IgG Fc receptor promoter region polymorphism is a key genetic element for murine systemic lupus erythematosus. (2010)
  • Author(s): Lin Q, Hou R, Sato A, Ohtsuji M, Ohtsuji N, Nishikawa K, Tsurui H, Amano H, Amano E, Sudo K, Nishimura H, Shirai T, Hirose S.
  • Journal Title: Autoimmunity Volume: 34 Pages: 356-63
  • Peer Reviewed
• [Journal Article] FTY720 exerts a survival advantage through the prevention of end-stage glomerular inflammation in Lupus-prone BXSB mice. (2010)
  • Author(s): Ando S, Amano H, Amano E, Minowa K, Watanabe T, Nakano S, Nakiri Y, Morimoto S, Tokano Y, Lin Q, Hou R, Ohtsuji M, Tsurui H, Hirose S, Takasaki Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 394 Pages: 804-810
  • Peer Reviewed
• [Journal Article] Evidence that Yaa-induced loss of marginal zone B cells is a result of dendritic cell-mediated enhanced activation. (2010)
  • Author(s): Santiago-Raber ML, Amano H, Amano E, Fossati-Jimack L, Swee LK, Rolink A, Izui S.
  • Journal Title: J Autoimmun. Volume: 34 Pages: 349-355
  • Peer Reviewed
• [Journal Article] Up-regulation of the endoplasmic reticulum transmembrane protein UNC93B in the B cells of patients with active systemic lupus erythematosus (2010)
  • Author(s): Nakano S, Morimoto S, Suzuki S, Watanabe T, Amano H, Takasaki Y.
  • Journal Title: Rheumatology(Oxford) (In print)
  • Peer Reviewed
• [Journal Article] Fcgamma receptor-dependent expansion of a hyperactive monocyte subset in lupus-prone mice (2009)
  • Author(s): Santiago-Raber ML, Amano H(equal contributor), Amano E, Baudino L, Otani M, Lin Q, Nimmerjahn F, Verbeek JS, Ravetch JV, Takasaki Y, Hirose S, Izui S
  • Journal Title: Arthritis Rheum Volume: 60(8) Pages: 2408-17
  • Peer Reviewed
• [Journal Article] SLEモデルマウスとYaa遺伝子 (2009)
  • Author(s): 天野浩文
  • Journal Title: リウマチ科 Volume: 42(2) Pages: 198-204
• [Journal Article] Fcgamma receptor-dependent expansion of a hyperactive monocyte subset in lupus-prone mice (2009)
  • Author(s): Santiago-Raber ML, Amano H, Amano E, Baudino L, Otani M, Lin Q, Nimmerjahn F, Verbeek JS, Ravetch JV, Takasaki Y, Hirose S, Izui S
  • Journal Title: Arthritis and Rheumatism 60(8) Pages: 2408-2417
  • Peer Reviewed
• [Journal Article] Inhibitory IgG Fc receptor promoter region polymorphism is a key genetic element for murine systemic lupus erythematosus (2009)
  • Author(s): Lin Q, Hou R, Sato A, Ohtsuji M, Ohtsuji N, Nishikawa K, Tsurui H, Amano H, Amano E, Sudo K, Nishimura H, Shirai T, Hirose S.
  • Journal Title: Journal of Autoimmunity (In print)
  • Peer Reviewed
• [Presentation] Yaa-Mutation induces phenotype shift from rheumatoid arthritis to systemic lupus enythematosus in FcgRIIB-deficient B6 mice (2011)
  • Author(s): Amano H, 他
  • Organizer: The 75^<th> National Meeting of American College of Rheumatology
  • Place of Presentation: USA, Chicago
  • Year and Date: 2011-11-05
• [Presentation] SLEとB細胞異常 (2011)
  • Author(s): 天野浩文
  • Organizer: 免疫疾患学会連合2011(日本臨床免疫学会総会)
  • Place of Presentation: 東京
  • Year and Date: 2011-09-16
• [Presentation] FTY720治療後のBXSBマウス腎炎における腎臓局所サイトカイン・ケモカインの発現の変化 (2011)
  • Author(s): 安藤誠一郎、天野浩文、天野恵理、箕輪健太郎、渡邉崇、仲野総一郎、森本真司、戸叶嘉明、林青順、侯蓉、大辻希樹、広瀬幸子、高崎芳成
  • Organizer: 第55回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] 活動期SLE患者において血清中sCD138は高値を示す (2011)
  • Author(s): 箕輪健太郎、天野浩文、仲野総一郎、安藤誠一郎、渡邉崇、名切裕、天野恵理、戸叶嘉明、森本真司、高崎芳成
  • Organizer: 第55回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] 当科におけるループス腎炎V型の治療と予後の検討 (2011)
  • Author(s): 森本真司、仲野総一郎、渡邉崇、天野浩文、高崎芳成
  • Organizer: 第55回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] 全身性エリテマトーデス剖検80例における病理所見と臨床経過に関する検討 (2011)
  • Author(s): 今高之、山路健、杉本郁、宮下知子、小笠原倫大、建部一夫、天野浩文、津田裕士、橋本博史、高崎芳成
  • Organizer: 第26回日本臨床リウマチ学会
  • Place of Presentation: 横浜
• [Presentation] Yaa-Mutation Induces Phenotype Shift From Rheumatoid Arthritis to Systemic Lupus Erythematosus in FcgRIIB-Deficient B6 Mice (2011)
  • Author(s): Amano H, Kawano S, Kaneko T, Sato-Hayashizaki A, Lin Q, Takasaki Y and Hirose S.
  • Organizer: The75th National Meeting of American College of Rheumatology
  • Place of Presentation: Chicago
• [Presentation] SLEとB細胞異常 (2011)
  • Author(s): 天野浩文, 安藤誠一, 箕輪健太郎, 金子俊之, 河野晋也, 仲野総一郎, 渡辺崇, 石原直樹, 天野恵理, 森本真司, 林青順, 広瀬幸子, 高崎芳成
  • Organizer: 第39回日本臨床免疫学会総会
  • Place of Presentation: 東京
• [Presentation] 成人still病の治療法についての検討 (2011)
  • Author(s): 渡邉崇, 他
  • Organizer: 第55回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] The role of complement and B cell antigen receptor on the development of marginal zone B cells in lupus-prone mice (2010)
  • Author(s): Amano H, Amano E, Ando S, Minowa K, Watanabe T, Nakano S, Morimoto S, Hirose S, Takasaki Y, Izui S.
  • Organizer: 14th Congress of the Asia Pacific League of Associations for Rheumatology(APLAR 2010)
  • Place of Presentation: Hong Kong
• [Presentation] The hidden activation of plasma cell in SLE patients detected by soluble CD138 (2010)
  • Author(s): Minowa K, Amano H, Nakano S, Ando S, Watanabe T, Ishihara N, Nakiri Y, Morimoto S, Tokano Y, Takasaki Y.
  • Organizer: 14th International Congress of Immunology Kobe
• [Presentation] The role of complement and B cell antigen receptor on the development of marginal zone B cells in lupus-prone mice (2010)
  • Author(s): Amano H, Amano E, Ando S, Minowa K, Morimoto S, Hirose S, Izui S, Takasaki Y.
  • Organizer: 14th International Congress of Immunology Kobe
• [Presentation] SLEモデルマウス脾臓辺縁帯B細胞形成における補体とB細胞抗原受容体の関与 (2010)
  • Author(s): 天野浩文、天野恵理、安藤誠一郎、箕輪健太郎、森本真司、戸叶嘉明、広瀬幸子、高崎芳成
  • Organizer: 第53回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] SLEモデルマウス脾臓辺縁帯B細胞形成における補体とB細胞抗原受容体の関与 (2010)
  • Author(s): 天野浩文、天野恵理、安藤誠一郎、箕輪健太郎、森本真司、戸叶嘉明、広瀬幸子、高崎芳成
  • Organizer: 第54回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] FTY720によるBXSBマウスのループス腎炎抑制機序の解析 (2010)
  • Author(s): 安藤誠一郎、天野浩文、天野恵理、渡邉崇、名切裕、森本真司、戸叶嘉明、林青順、大辻希樹、広瀬幸子、高崎芳成
  • Organizer: 第54回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] Toll-like receptor(TLR)とリウマチ性疾患(シンポジウム) (2009)
  • Author(s): 天野浩文、天野恵理、仲野総一郎、安藤誠一郎、箕輪健太郎、渡辺崇、森本真司、林青順、広瀬幸子、戸叶嘉明、高崎芳成
  • Organizer: 第53回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Toll-like receptor(TLR)とリウマチ性疾患 (2009)
  • Author(s): 天野浩文
  • Organizer: 第53回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京