CD40/CD40L interactions in a mouse model of systemic sclerosis

• Project/Area Number: 19790793
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: Kanazawa University (2008); Nagasaki University (2007)
• Principal Investigator: KOMURA Kazuhiro Kanazawa University, 附属病院, 助教 (50401914)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,650,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 全身性強皮症 / 治療 / 線維化 / 自己免疫 / モノクローナル抗体 / 動物モデル / 免疫治療

Research Abstract

強皮症モデルマウスであるタイトスキンマウスに抗CD40L抗体を投与した。その結果、タイトスキンマウスの皮膚硬化が現弱し、免疫活性化状態も正常化した。従って、タイトスキンマウスの皮膚硬化と免疫活性化状態にCD40/CD40L相互作用が関与する事が示唆された。既に、抗CD40L抗体は自己免疫性血小板減少症などに対する使用実績が有るため、今後、全身性強皮症においても新しい治療薬として有用である可能性が考えられた。さらに、全身性強皮症以外の線維化を来す疾患群に対する治療応用も期待された。

Research Products

• [Journal Article] Clinical Significance of Serum Hyaluronan Levels in Systemic Sclerosis : Association with Disease Severity. (2008)
  • Author(s): Yoshizaki A, Komura K, et al.
  • Journal Title: J Rheumatol. Sep;35(9) Pages: 1825-9
  • Peer Reviewed
• [Journal Article] Increased Serum Soluble. OX40 in Patients with Systemic Sclerosis. (2008)
  • Author(s): Komura K, et al.
  • Journal Title: J Rheumatol. 35(12) Pages: 2359-62
  • Peer Reviewed
• [Journal Article] CD19 Regulates the Development of Bleomycin-induced Pulmonary Fibrosis. (2008)
  • Author(s): Komura K, et al.
  • Journal Title: Arthritis & Rheumatism. 58(11) Pages: 3574-84
  • Peer Reviewed
• [Journal Article] Autoantibodies against matrix metalloproteinase-1 in patients with localized scleroderma. (2008)
  • Author(s): Tomimura S, Komura K, et al.
  • Journal Title: J Dermatol Sci. 52(1) Pages: 47-54
  • NAID: 10024457305
  • Peer Reviewed
• [Journal Article] Involvement of gaseous low molecular monoxides in the cutaneous reverse passive Arthus reaction : cytoprotective action of carbon monoxide. (2008)
  • Author(s): Shimizu K, Komura K, et al.
  • Journal Title: Clin Exp Immunol. 153(2) Pages: 245-257
  • NAID: 120006983393
  • Peer Reviewed
• [Journal Article] CD19 regulates skin and lung fibrosis via Toll-like receptor signaling in a model of bleomycin-induced scleroderma. (2008)
  • Author(s): Yoshizaki A, Komura K, et al.
  • Journal Title: Am J Pathol. 172(6) Pages: 1650-63
  • Peer Reviewed
• [Journal Article] Clinical association of serum interleukin-17 levels in systemic sclerosis : is systemic sclerosis a Th17 disease? (2008)
  • Author(s): Murata M, Komura K, et al.
  • Journal Title: J Dermatol Sci. 50(3) Pages: 240-2
  • NAID: 10024119233
  • Peer Reviewed
• [Journal Article] Anti-p53 Autoantibody in Systemic Sclerosis : Association with Limited Cutaneous Systemic Sclerosis. (2008)
  • Author(s): Hara T, Komura K, et al.
  • Journal Title: J Rheumatol. 35(3) Pages: 451-7
  • Peer Reviewed
• [Journal Article] Elevation of Serum Lymphotactin Levels in Patients with Systemic Sclerosis. (2008)
  • Author(s): Muroi E, Komura K, et al.
  • Journal Title: J Rheumatol. 35(5) Pages: 834-8
  • Peer Reviewed
• [Journal Article] Correlation of IgE autoantibody to BP180 with a severe form of bullous pemphigoid. (2008)
  • Author(s): Iwata Y, Komura K, et al.
  • Journal Title: Arch Dermatol. 144(1) Pages: 41-8
  • Peer Reviewed
• [Journal Article] The clinical relevance of serum antinuclear antibodies in Japanese patients with systemic sclerosis. (2008)
  • Author(s): Hamaguchi Y, Komura K, et al.
  • Journal Title: Br J Dermatol. 158(3) Pages: 487-95
  • Peer Reviewed
• [Journal Article] The Elevation of IgG Levels Is a Serological Indicator for Pulmonary Fibrosis in Systemic Sclerosis with Anti-topoisomerase I Antibodies. (2008)
  • Author(s): Komura K, Sato S.
  • Journal Title: Clin Exp Dermatol. 33(3) Pages: 329-32
  • Peer Reviewed
• [Journal Article] Increased Serum IL-23 Levels in Systemic Sclerosis. (2008)
  • Author(s): Komura K, et al.
  • Journal Title: J Rheumatol. 35(1) Pages: 120-5
  • Peer Reviewed
• [Journal Article] Blockade of CD40-CD40 ligand interactions attenuates skin fibrosis and autoimmunity in the tight-skin mouse. (2008)
  • Author(s): Komura K, et al.
  • Journal Title: Ann Rheum Dis. 67(6) Pages: 867-72
  • NAID: 120006984197
  • Peer Reviewed
• [Journal Article] 接触皮膚炎では、塩酸エピナスチンはE-セレクチンの機能を抑制する. (2008)
  • Author(s): 小村一浩, ほか
  • Journal Title: 薬理と治療 36巻1号 Pages: 33-37
  • Peer Reviewed
• [Journal Article] マウス接触性皮膚炎において、ロラタジンはPSGL-1の機能を抑制する(原著論文) (2008)
  • Author(s): 吉崎歩, 小村一浩, ほか
  • Journal Title: 臨牀と研究 (0021-4965)85巻12号 Pages: 1755-1759
  • Peer Reviewed
• [Journal Article] 小児発症の好酸球性筋膜炎の1例 (2008)
  • Author(s): 鍬塚大, 小村一浩, ほか
  • Journal Title: 西日本皮膚科 70巻6号 Pages: 614-617
  • NAID: 10024944497
  • Peer Reviewed
• [Journal Article] 若年性全身性強皮症の3例 (2008)
  • Author(s): 鍬塚大, 小村一浩, ほか
  • Journal Title: 西日本皮膚科 70巻4号 Pages: 371-376
  • NAID: 10024943904
  • Peer Reviewed
• [Journal Article] クリオフィブリノーゲンが増悪因子であった難治性下腿潰瘍の1例 (2008)
  • Author(s): 岡崎志帆子,小村一浩, ほか
  • Journal Title: 皮膚科の臨床 50巻4号 Pages: 459-462
  • Peer Reviewed
• [Journal Article] 足底のDiscoid Lupus Erythematosus皮疹上に生じたSquamous Cell Carcinomaの1例 (2008)
  • Author(s): 横山洋子, 小村一浩, ほか
  • Journal Title: 西日本皮膚科 70巻1 Pages: 23-26
  • NAID: 10024943159
  • Peer Reviewed
• [Journal Article] Blockade of CD40-CD40 ligand interactions attenuates skin fibrosis and autoimmunity in the tight-skin mouse (2008)
  • Author(s): Komura K et.al.
  • Journal Title: Ann Rheum Dis 67(6) Pages: 867-72
  • NAID: 120006984197
  • Peer Reviewed
• [Journal Article] Endothelial selectins regulate skin wound healing in cooperation with L-selectin and ICAM-1. (2007)
  • Author(s): Yukami T, Komura K, et al.
  • Journal Title: J Leukoc Biol. 82(3) Pages: 519-31
  • Peer Reviewed
• [Journal Article] Antigen specificity of antihistone antibodies in connective tissue disease patients with anti-U1RNP antibodies. (2007)
  • Author(s): Wayaku T, Komura K, et al.
  • Journal Title: Rheumatol Int. 28(2) Pages: 113-9
  • Peer Reviewed
• [Journal Article] Increased serum levels of nitrotyrosine, a marker for peroxynitrite production, in systemic sclerosis. (2007)
  • Author(s): Shimizu K, Komura K, et al.
  • Journal Title: Clin Exp Rheumatol. 25(2) Pages: 281-6
  • Peer Reviewed
• [Journal Article] BAFF Antagonist Attenuates the Development of Skin Fibrosis in Tight-Skin Mice. (2007)
  • Author(s): Matsushita T, Komura K, et al.
  • Journal Title: J Invest Dermatol. 127(12) Pages: 2772-80
  • NAID: 120005756483
  • Peer Reviewed
• [Journal Article] Autoantibody against peroxiredoxin I, an antioxidant enzyme, in patients with systemic sclerosis : possible association with oxidative stress. (2007)
  • Author(s): Iwata Y, Komura K, et al.
  • Journal Title: Rheumatology. 46(5) Pages: 790-5
  • Peer Reviewed
• [Journal Article] Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis : an association with malignancy. (2007)
  • Author(s): Kaji K, Komura K, et al, Takehara K.
  • Journal Title: Rheumatology 46(1) Pages: 25-8
  • Peer Reviewed
• [Journal Article] Blockade of CD40-CD40 Ligand Interactions Attenuates Skin Fibrosis and Autoimmunity in the Tight-skin Mouse (2007)
  • Author(s): Komura K, et. al.
  • Journal Title: Ann Rheumatic Dis On-line Pages: 10-10
  • NAID: 120006984197
  • Peer Reviewed
• [Journal Article] Increased serum soluble CD40 levels in patients with systemic sclerosis. (2007)
  • Author(s): Komura K, et. al.
  • Journal Title: J Rheumatol 34(2) Pages: 353-358
  • Peer Reviewed
• [Presentation] Blockade of CD40-CD40 Ligand Interactions Attenuates Skin Fibrosis and Autoimmunity in the Tight-skin Mouse. (2007)
  • Author(s): Komura K et al.
  • Organizer: Fedaration of Clinical Immunology Societies
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2007-06-07
• [Presentation] Blockade of CD40-CD40 Ligand Interactions Attenuates Skin Fibrosis and Autoimmunity in the Tight-skin Mouse (2007)
  • Author(s): Komura K, et. al.
  • Organizer: Fedaration of Clinical Immunology Societies
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2007-06-07
• [Book] 全身性強皮症の治療 (2008)
  • Author(s): 小村一浩
  • Publisher: Derma
• [Book] 紫外線による免疫制御 (2008)
  • Author(s): 小村一浩
  • Publisher: 日本臨床免疫学会雑誌