Exploring inhibitory mechanisms of autoinflammation by macrophage in arthritis

• Project/Area Number: 24591440
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: University of Tsukuba
• Principal Investigator: MATSUMOTO Isao 筑波大学, 医学医療系, 准教授 (30343081)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 関節リウマチ / 炎症性サイトカイン / 炎症制御 / 単球 / 好中球 / シトルリン化タンパク抗体 / GPI / ＴＮＦ誘導蛋白 / シトルリン化タンパク / ＡＣＰＡ / ＧＰＩ / TNF誘導蛋白 / 自己抗体 / ACPA / 関節炎

Outline of Final Research Achievements

We identified TNF-induced protein such as TIARP from active arthritic mice. TIARP-deficient mice spontaneously develop arthritis, and their expression is localized in monocytes, neutrophil and fibroblast in mice and humans. In humans, their expression in PBMC is clearly regulated by TNF and IL-6 inhibitors, and related to the therapeutic response. In addition, anti-citrullinated GPI-peptide antibodies were specifically identified in patients with RA, and correlated to disease activity, possibly belongs to one of the new biomarkers in RA.

Research Products

• [Journal Article] Specific overexpression of TNFAIP9 in CD14+CD16- monocytes in patients with rheumatoid arthritis- Comparative analysis with TNFAIP3. (2015)
  • Author(s): 115.Takai C, *Matsumoto I, Inoue A, Umeda N, Tanaka Y, Kurashima Y, Wada Y, Narita I, Sumida T.
  • Journal Title: Clin Exp Immunol Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulatory roles of tumor necrosis factor alpha-induced proteins (TNFAIP) 3 and 9 in arthritis. (2014)
  • Author(s): 10.*Matsumoto I, Inoue A, Takai C, Umeda N, Tanaka Y, Kurashima Y, Sumida T.
  • Journal Title: Clin Immunol Volume: 153 Pages: 73-78
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulatory roles of tumor necrosis factor alpha-induced proteins (TNFAIP) 3 and 9 in arthritis. (2014)
  • Author(s): *Matsumoto I, Inoue A, Takai C, Umeda N, Tanaka Y, Kurashima Y, Sumida T.
  • Journal Title: Clinical Immunology Volume: in press
  • Peer Reviewed
• [Journal Article] Antigen-specific overexpression of human cartilage glycoprotein 39 on CD4+CD25+Foxp3+ Treg cells in the generation of glucose-6-phosphate isomerase induced arthritis. (2014)
  • Author(s): Tanaka Y, *Matsumoto I, Inoue A, Umeda N, Takai C, Sumida T.
  • Journal Title: Clinical Experimental Immunology Volume: in press
  • Peer Reviewed
• [Journal Article] Anti-citrullinated glucose-6-phosphate isomerase peptide antibodies in patients with rheumatoid arthritis are associated with HLA-DRB1 shared epitope alleles and disease activity. (2013)
  • Author(s): Umeda N, *Matsumoto I, Ito I, Kawasaki A, Tanaka Y, Inoue A, Tanaka Y, Tsuboi H, Suzuki T, Hayashi T, Ito S, Tsuchiya N, Sumida T.
  • Journal Title: Clin. Exp. Immunol. Volume: 172 Pages: 44-53
  • Peer Reviewed
• [Journal Article] TIARP (TNFAIP9) deficiency leads to arthritis via IL-6 overproduction with enhanced NF-kB, STAT3 signaling and dysregulated apoptosis of macrophages. (2012)
  • Author(s): Inoue A, *Matsumoto I, Tanaka Y, Umeda N, Tanaka Y, Mihara M, Takahashi S, Sumida T.
  • Journal Title: Arthritis Rheum Volume: 64 Issue: 12 Pages: 3877-85
  • DOI: 10.1002/art.34666
  • Peer Reviewed
• [Journal Article] Six-transmembrane epithelial antigen of prostate4(STEAP4) is expressed on monocytes/neutrophils, and is regulated by TNF antagonist in patients with rheumatoid arthritis. (2012)
  • Author(s): Tanaka Y, *Matsumoto I, Iwanami K, Inoue A, Umeda N, Tanaka Y, Sugihara M, Hayashi T, Ito S, Sumida T:
  • Journal Title: Clin. Exp. Rheumatol. Volume: 30 Pages: 99-102
  • Peer Reviewed
• [Presentation] リウマチ性疾患モデルをどのように臨床に生かすか？ (2015)
  • Author(s): 松本功
  • 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 – 2015-04-25
  • Invited
• [Presentation] Biological action of anti-TNF therapy in the pathogenesis of rheumatoid arthritis-CZP and the beyond (2014)
  • Author(s): 松本功
  • Organizer: 第43回日本免疫学会総会・学術集会クリニカルセミナー
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
  • Invited
• [Presentation] RAの早期診断・治療における小関節炎の評価―イメージングモダリティを含めて (2014)
  • Author(s): 松本功
  • Organizer: 第58回日本リウマチ学会総会・学術集会 ランチョンセミナー
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24 – 2014-04-26
  • Invited
• [Presentation] Role of IL-6 and TNFa-induced proteins in autoimmune arthritis
  • Author(s): Matsumoto I
  • Organizer: JSICR and MMCB
  • Place of Presentation: Tokyo
  • Invited
• [Presentation] The regulatory role of TNFα-induced protein9(TNFAIP9) in arthritis with mice and humans.
  • Author(s): Matsumoto I
  • Organizer: Autoimmunity Congress Asia 2013
  • Place of Presentation: Hong Kong
  • Invited
• [Presentation] Autoimmune arthritis mediated by glycolytic enzyme- focusing on regulatory TNFa-induced protein
  • Author(s): Matsumoto I
  • Organizer: International Congress on Autoimmunology
  • Place of Presentation: Granada, Spain
  • Invited
• [Presentation] Pathophysiology of autoimmune arthritis - From clinic to bench and vice versa-
  • Author(s): Matsumoto I
  • Organizer: 第56回日本リウマチ学会総会（東京）国際シンポジウム
  • Place of Presentation: Tokyo, Japan
  • Invited
• [Presentation] Immunological mechanisms in autoimmune arthritis via ubiquitous autoantigens.
  • Author(s): Matsumoto I, Sumida T
  • Organizer: 第56回日本リウマチ学会総会（東京）国際シンポジウム
  • Place of Presentation: Tokyo Japan
  • Invited
• [Book] Pharma Medica (2013)
  • Author(s): 松本 功
  • Publisher: サイトカインに対する生物学的製剤 自己免疫疾患の最近の話題と展望
• [Book] 特集：関節リウマチ(RA): 診断と治療の進歩 病態 関節炎モデル (2012)
  • Author(s): 松本 功
  • Publisher: 日本内科学会雑誌
• [Remarks] 筑波大学 膠原病・リウマチ・アレルギー内科
  • URL: http://www.md.tsukuba.ac.jp/clinical-med/rheumatology/
• [Remarks] 筑波大学膠原病内科のページ
  • URL: http://www.md.tsukuba.ac.jp/clinical-med/rheumatology/