B cell depletion therapy for the model mouse of scleroderma
| Project/Area Number |
18591238
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kanazawa University |
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Principal Investigator |
HASEGAWA Minoru Kanazawa University, Kanazawa University Hospital, Instructor (50283130)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Tight skin mouse / systemic sclerosis / B cell / CD20 / aintbody-therapy / cytokine / fibrosis / autoimmunity / 自己抗体 |
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| Research Abstract |
Systemic sclerosis (scleroderma) is an autoimmune disease characterized by excessive extracellular matrix deposition in the skin. Although autoantibody production correlates with skin sclerosis, a direct role for B lymphocytes in disease development or progression has remained controversial. To address this issue, skin sclerosis and autoimmunity was assessed in tight-skin mice, a genetic model of human systemic sclerosis, following circulating and tissue B cell depletion using an anti-mouse CD20 mAb before and after disease development. CD20 mAb treatment (10-20 rig) depleted the majority (85-99%) of circulating and tissue B cells in newborn and adult tight-skin mice. Dose-dependent B cell depletion in newborn tight-skin mice significantly suppressed (-43%) the development of skin fibrosis and hypergammaglobulinemia, and abrogated rheumatoid factor and autoantibody production. B cell depletion in young tight-skin mice also restored a more normal balance between Th1 and Th2 cytokine mRNA expression in the skin and spleen. By contrast, effective B cell depletion did not affect skin fibrosis, hypergammaglobulinemia, rheumatoid factor and autoantibody levels in adult mice with established disease. Thereby, B cell depletion during disease onset suppressed skin fibrosis, indicating that B cells contribute to the initiation of systemic sclerosis pathogenesis in tight-skin mice but are not required for disease maintenance.
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis2006
Author(s)
Minoru Hasegawa, Yasuhito Hamaguchi, Koichi Yanaba, Jean-David Bouaziz, Junji Uchida, Manabu Fujimoto, Takashi Matsushita, Yukiyo Matsushita, Mayuka Horikawa, Kazuhiro Komura, Kazuhiko Takehara, Shinichi Sato, Thomas F. Tedder
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Journal Title
Am J Pathol 169
Pages: 954-966
Description
「研究成果報告書概要(欧文)」より
Related Report
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