Induction of Autoimmunity in a Bleomycin-Induced Murine Model of Experimental Systemic Sclerosis: An Important Role for CD4+ T Cells

Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Journal of Investigative Dermatology (Impact Factor: 6.37). 02/2009; 129(7):1688-95. DOI: 10.1038/jid.2008.431
Source: PubMed

ABSTRACT Systemic sclerosis (SSc) is an autoimmune disease characterized by the excessive deposition of collagen in the skin or other organs and the production of specific antinuclear antibodies (ANAs). Recently, bleomycin (BLM)-induced experimental scleroderma was reported in a murine model. Here, we present further development of this model and suggest that it is appropriate for the analysis of human diffuse type SSc. BLM was injected into the shaved backs of C3H or BALB/c mice (100 microg/mouse) 5 days per week for 3 weeks. Skin fibrosis was confirmed and pathological changes were seen in the lower part of the esophagus and stomach similar to those seen in SSc. The sera from these mice had autoantibodies specific to the damaged tissues and ANAs. Transfer of CD4(+) T cells from BLM-treated BALB/c mice induced the same pathological changes and antibody production in untreated-BALB/c nude mice. Hence, tissue fibrosis and the production of ANAs are probably associated with CD4(+) T-cell activity in this model. In conclusion, this model will be valuable for investigating the relationship between tissue fibrosis and abnormalities of the immune system.

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    • "In addition, following the administration of very high doses of subcutaneous bleomycin, lung fibrosis with cellular infiltrates and damaged lung architecture appeared [141]. Antinuclear autoantibodies, such as anti-Scl-70, anti-U1-RNP, and anti-histone also reflect the development of a systemic immune reaction [142]. "
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