Document Detail


B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis.
MedLine Citation:
PMID:  16936269     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Systemic sclerosis (scleroderma) is an autoimmune disease characterized by excessive extracellular matrix deposition in the skin. A direct role for B lymphocytes in disease development or progression has remained controversial, although autoantibody production is a feature of this disease. To address this issue, skin sclerosis and autoimmunity were assessed in tight-skin mice, a genetic model of human systemic sclerosis, after circulating and tissue B-cell depletion using an anti-mouse CD20 monoclonal antibody before (day 3 after birth) and after disease development (day 56). CD20 monoclonal antibody treatment (10 to 20 microg) depleted the majority (85 to 99%) of circulating and tissue B cells in newborn and adult tight-skin mice by days 56 and 112, respectively. B-cell depletion in newborn tight-skin mice significantly suppressed (approximately 43%) the development of skin fibrosis, autoantibody production, and hypergammaglobulinemia. B-cell depletion also restored a more normal balance between Th1 and Th2 cytokine mRNA expression in the skin. By contrast, B-cell depletion did not affect skin fibrosis, hypergammaglobulinemia, 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.
Authors:
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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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of pathology     Volume:  169     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-28     Completed Date:  2006-10-24     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  954-66     Citation Subset:  AIM; IM    
Affiliation:
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan.
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MeSH Terms
Descriptor/Qualifier:
Aging / genetics,  immunology,  pathology
Animals
Antibodies, Monoclonal / pharmacology
Antibody Formation / genetics,  immunology*
Antigens, CD20 / immunology
Autoantibodies / immunology*
Autoimmunity / genetics,  immunology*
B-Lymphocytes / immunology*,  pathology
Cytokines / genetics,  immunology
Disease Models, Animal
Female
Fibrosis / genetics,  immunology,  pathology
Gene Expression Regulation / genetics,  immunology
Humans
Lymphocyte Depletion / methods
Mice
Mice, Knockout
RNA, Messenger / genetics,  immunology
Scleroderma, Systemic / genetics,  immunology*,  pathology
Skin / immunology,  pathology
Th1 Cells / immunology,  pathology
Th2 Cells / immunology,  pathology
Grant Support
ID/Acronym/Agency:
AI56363/AI/NIAID NIH HHS; CA105001/CA/NCI NIH HHS; CA96547/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD20; 0/Autoantibodies; 0/Cytokines; 0/RNA, Messenger
Comments/Corrections

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