Article

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: 6.19). 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.

0 0
 · 
0 Bookmarks
 · 
60 Views
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: The antineoplastic drug bleomycin leads to the side effect of pulmonary fibrosis in both humans and mice. We challenged genetically diverse inbred lines of mice from the Collaborative Cross with bleomycin to determine the heritability of this phenotype. Sibling pairs of mice from 40 lines were treated with bleomycin. Lung disease was assessed by scoring lung pathology and by measuring soluble collagen levels in lavage fluid. Serum micro ribonucleic acids (miRNAs) were also measured. Inbred sibling pairs of animals demonstrated high coinheritance of the phenotypes of disease susceptibility or disease resistance. The plasma levels of one miRNA were clearly correlated in sibling mice. The results showed that, as in humans, the lines that comprise the Collaborative Cross exhibited wide genetic variation in response to this drug. This finding suggests that the genetically diverse Collaborative Cross animals may reveal drug effects that might be missed if a study were based on a conventional mouse strain.
    Pharmacogenomics and Personalized Medicine 01/2011; 4:35-45.
  • [show abstract] [hide abstract]
    ABSTRACT: Pulmonary fibrosis is a devastating disease that affects millions of people worldwide. Among the most common forms of lung fibrosis are idiopathic pulmonary fibrosis (IPF) and scleroderma-related interstitial lung disease (SSc-ILD). Despite a wealth of literature regarding each of these diseases, studies that directly compare IPF and SSc-ILD are rare. This review compares the salient features of IPF and SSc-ILD. Clinical presentation and demographics will be presented, along with the newly released radiographic and pathologic criteria for IPF. Evolving concepts of pathogenesis including the role of structural cell injury, the pathogenic role of macrophages and lymphocytes, and the origin of fibroblasts are described. We conclude with new developments in the search for predictive biomarkers of disease progression, such as markers of epithelial injury, lymphocyte subsets, and circulating fibrocytes, will be presented. We conclude with a discussion of the results of recent clinical trials. It is found that despite differences in clinical presentation and response to treatment, similarities are noted in proposed pathogenesis and putative biomarkers. It is hoped that this information will lead to studies aimed at understanding the factors driving these difficult to treat and often deadly diseases.
    Current opinion in rheumatology 09/2012; 24(6):656-62. · 4.60 Impact Factor
  • Source
    02/2012; , ISBN: 978-953-307-869-4

Full-text

View
0 Downloads
Available from

Hideaki Ishikawa