Effect of SLAM mutation and activating and inhibitory FcR on autoimmune prone mice

• Project/Area Number: 26461474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Juntendo University
• Principal Investigator: TAKASAKI Yoshinari 順天堂大学, 医学部, 特任教授 (80154772)
• Co-Investigator(Kenkyū-buntansha): 天野 浩文 順天堂大学, 医学部, 准教授 (50318474)
• Co-Investigator(Renkei-kenkyūsha): HIROSE Sachiko 桐蔭横浜大学, 工学部, 客員研究員 (00127127)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: SLE / Slam / Yaa / Fc receptor / モデルマウス / 全身性エリテマトーデス / 疾患モデルマウス / 遺伝子 / 自己免疫疾患 / Fcレセプター / 関節リウマチ / Slam遺伝子 / Yaa遺伝子

Outline of Final Research Achievements

We previously obtained a 129-derive FcγRIIB-deficient C57BL/6 (B6) congenic strain of mice, which developed rheumatoid arthritis (RA). The introduction of the Yaa (Y-linked autoimmune acceleration) mutation (Tlr7 gene duplication) to the FcγRIIB-deficient B6 mice(B6.FcγRIIB-/-.Yaa ) developed lupus like nephritis but not RA. By extensive backcrossing, we established wildtype FcγRIIB and 129-derive autoimmune-prone SLAM haplotype(Slam129). We examined the phenotype of the mice, and also Slam129.Yaa mice by introducing Yaa mutation. Slam129 mice did not show any pathogenic autoantibodies. When introducing Yaa mutation, Slam129.Yaa mice showed significant increase the serum levels of anti-RNP/Sm antibodies. They did not show the elevation of anti-dsDNA antibodies. Also they developed nephritis but the pathological score was significantly lower than B6.FcγRIIB-/-.Yaa mice. Autoimmune-prone Slam129.Yaa mice developed specific lupus phenotype resembling mixed connective tissue disease.

Research Products

• [Journal Article] Disease flare patterns and predictors of systemic lupus erythematosus in a monocentric cohort of423 Japanese patients during a long-term follow-up:The JUDE study. (2017)
  • Author(s): Minowa K,Amano H,Ando S,Watanabe T,Ogasawara M,Kawano S, Kaneko T,Morimoto S,Yamaji K,Tamura N,Tokano Y,Hashimoto H,Takasaki Y.
  • Journal Title: Mod Rheumatol. Volume: 27 Issue: 1 Pages: 72-76
  • DOI: 10.1080/14397595.2016.1192745
  • Peer Reviewed / Open Access
• [Journal Article] Independent Association of HLA-G 3’ Untranslated Region 14bp Indel Polymorphism with Systemic Lupus Erythematosus in a Japanese Population: a Case-control Association Study. (2016)
  • Author(s): Hachiya Y, Kawasaki A, Oka S, Kondo Y, Ito S, Matsumoto I, Kusaoi M, Amano H, Suda A, Setoguchi K, Nagai T,Shimada K, Sugii S, Okamoto A, Chiba N, Suematsu E, Ohno S, Katayama M, Kono H, Hirohata S, Takasaki Y, Hashimoto H, Sumida T, Nagaoka S, Tohma S, Furukawa H, Tsuchiya N.
  • Journal Title: PLoS ONE. Volume: 11 Issue: 6 Pages: 22-22
  • DOI: 10.1371/journal.pone.0158065
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Second-to-fourth Digit Ratio in Systemic Lupus Erythematosus (2015)
  • Author(s): Doe K, Nozawa K, Hirai T, Tsushima H, Hayashi E, Hiruma K, Ando S, Nakano S, Kon T, Amano H, Yamaji K, Tamura N, Takasaki Y
  • Journal Title: J Rheumatol Volume: 42 Issue: 5 Pages: 826-8
  • DOI: 10.3899/jrheum.140974
  • Peer Reviewed
• [Journal Article] Transcatheter Arterial Coil Embolization of Ruptured Common Hepatic Artery Aneurysm in a Patient with Behçet's Disease (2015)
  • Author(s): Hotta A, Kuwatsuru R, Asahi K, Okada S, Tsuge D, Shiraishi A, Takasaki Y
  • Journal Title: Case Rep Radiol Volume: 790175 Pages: 1-3
  • DOI: 10.1155/2015/790175
  • Peer Reviewed
• [Journal Article] Predictive value of bone destruction and duration of clinical remission for subclinical synovitis in rheumatoid arthritis patients (2015)
  • Author(s): Tokai N, Ogasawara M, Gorai M, Matsuki Y, Yamada Y, Murayama G, Sugisaki N, Nemoto T, Ando S, Minowa K, Kon T, Tada K, Matsushita M, Yamaji K, Tamura N, Makino S, Takasaki Y
  • Journal Title: Mod Rheumatol Volume: 25 Issue: 4 Pages: 540-5
  • DOI: 10.3109/14397595.2014.987421
  • Peer Reviewed
• [Journal Article] Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis (2015)
  • Author(s): Nakano S, Morimoto S, Suzuki S, Tsushima H, Yamanaka K, Sekigawa I, Takasaki Y
  • Journal Title: Rheumatology (Oxford) Volume: 54 Issue: 8 Pages: 1498-506
  • DOI: 10.1093/rheumatology/keu528
  • Peer Reviewed
• [Journal Article] Assessment of risks for pulmonary infection during 12 months after commencing or intensifying immunosuppressive treatment for active connective tissue diseases: A report from a large-scale prospective cohort study (2015)
  • Author(s): Yamazaki H, Sakai R, Koike R, Miyazaki Y, Tanaka M, Nanki T, Watanabe K, Yasuda S, Kurita T, Kaneko Y, Tanaka Y, Nishioka Y, Takasaki Y, Nagasaka K, Nagasawa H, Tohma S, Dohi M, Sugihara T, Sugiyama H, Kawaguchi Y, Inase N, Ochi S, Hagiyama H, Kohsaka H, Miyasaka N, Harigai M
  • Journal Title: Journal of Rheumatology Volume: 42 Issue: 4 Pages: 614-622
  • DOI: 10.3899/jrheum.140778
  • Peer Reviewed
• [Presentation] Inhibitory IgG Fc Receptor IIB on B cells and monocytes independently controls Yaa-induced murine lupus. (2016)
  • Author(s): Qingshun Lin,Hiromichi Tsurui,Hirofumi Amano,Keiko Nishikawa,Mareki Otsuji,Hiroyuki Nishimura, J.Sjef Verbeek, Sachiko Hirose.
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄
  • Year and Date: 2016-12-05
• [Presentation] Blocking of CD11b+cell-migration ameliorates rheumatoid arthritis-like disease spontaneously occurring in a unique FcRIIB-deficient mouse model. (2016)
  • Author(s): Mareki Otsuji,Qingshun Lin,Hideki Okazaki,Shuri Ikeda, Hinako Sasa-ki,Hirofumi Amano,Hideo Yagita,Hiroyuki Nishimura,Sachiko Hirose.
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄
  • Year and Date: 2016-12-05
• [Presentation] Role of Mucosal-associated Invariant T(MAIT)Cells In Lupus Dermatitis. (2016)
  • Author(s): Goh Murayama,Asako Chiba,Hirofumi Amano,Ken Yamaji, Naoto Tamu-ra,Sachiko Miyake.
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄
  • Year and Date: 2016-12-05
• [Presentation] 日本人全身性エリテマトーデスとHLA-G多型の関連 (2016)
  • Author(s): 川崎綾,八谷有紀, 古川宏,近藤裕也,伊藤聡,松本功,草生真規雄,天野浩文,須田昭子,長岡章平,瀬戸口京吾,永井立夫,廣畑俊成, 島田浩太,杉井章二, 岡本亨, 千葉実行,末松栄一,大野滋,片岡雅夫, 岡本明子,河野肇, 髙崎芳成,橋本博史,住田孝之, 當間重人, 土屋尚之
  • Organizer: 第60回日本リウマチ学会総会・学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-04-21
• [Presentation] 全身性エリテマトーデス患者における酸化ストレスマーカーd-ROMsと抗酸化力BAP (2016)
  • Author(s): 安藤誠一郎,天野浩文,浅井悠貴、山路健, 田村直人, 髙崎芳成
  • Organizer: 第60回日本リウマチ学会総会・学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-04-21
• [Presentation] Mechanism of phenotype conversion from rheumatoid arthritis to lupus in FcγRIIB-deficient C57BL/6 Yaa mice (2015)
  • Author(s): Kawano S, Amano H, Q.Lin, Nishikawa K, H.T.Tsurui, Shirai T, Hirose S, Takasaki Y
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: ローマ、イタリア
  • Year and Date: 2015-06-10
  • Int'l Joint Research
• [Presentation] LILRA4多型と全身性エリテマトーデスの関連の検討 (2015)
  • Author(s): 川崎 綾, 古川 宏, 近藤裕也, 伊藤 聡, 松本 功, 草生真規雄, 天野浩文, 須田昭子, 長岡章平, 瀬戸口京吾, 永井立夫, 廣畑俊成, 島田浩太, 杉井章二, 岡本 亨, 千葉実行, 末松栄一, 大野 滋, 片岡雅夫, 岡本明子, 河野 肇, 髙崎芳成, 橋本博史, 住田孝之, 當間重人, 土屋尚之
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-23
• [Presentation] 全身性エリテマトーデス患者における腹水貯留に関する検討 (2015)
  • Author(s): 今 高之, 塚原隆伊, 安倍俊之, 安藤誠一郎, 多田久里守, 建部一夫, 天野浩文, 山路 健, 田村直人, 髙崎芳成
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-23
• [Presentation] 抗リン脂質抗体がSLEの病型に与える影響について (2015)
  • Author(s): 山田祐介, 野澤和久, 天野浩文, 関川 巌, 髙崎芳成
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-23
• [Presentation] 劇症型A群連鎖球菌による蜂窩織炎を発症した結節性多発動脈炎の一例 (2015)
  • Author(s): 塚原隆伊, 多田久里守, 天野浩文, 山路 健, 田村直人, 髙崎芳成
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-23