期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 38, 期 7, 页码 1948-1960出版社
WILEY
DOI: 10.1002/eji.200837925
关键词
Congenic; IFN; systemic lupus erythematosus
类别
资金
- NIAID NIH HHS [R01 AI054902, U19 AI057234-03, U19 AI057234-02, R01 AI045196-02, R01 AI068842-04, P01 AI039824-020001, R01 AI068842-02, R01 AI068842-03, U19 AI057234-05, U19 AI057234-04, U19 AI 057234, P01 AI039824, R01 AI068842, R37 AI045196-06, R01 AI 068842, U19 AI057234-01, R37 AI045196, U19 AI057234, R01 AI068842-01, U19 AI057234-05S1, R01 AI045196, R01 AI054902-01, R01 AI069371-01, R01 AI069371, U19 AI057234-010005] Funding Source: Medline
- NIAMS NIH HHS [P50 AR054083-019001, P50 AR054083-029001, P50 AR054083-010001, P50 AR 054083, P50 AR054083-030001, P50 AR054083-01, P50 AR054083, P50 AR054083-020001, P50 AR054083-03, P50 AR054083-02] Funding Source: Medline
The impact of IFN-alpha secretion on disease progression was assessed by comparing phenotypic changes in the lupus-prone B6.Sle1Sle2Sle3 (B6.Sle123) strain and the parental C57BL/6 (B6) congenic partner using an adenovirus (ADV) expression vector containing a recombinant IFN-a gene cassette (IFN-ADV). A comprehensive comparison of cell lineage composition and activation in young B6 and B6.Sle123 mice revealed a variety of cellular alterations in the presence and absence of systemic IFN-alpha. Most IFN-alpha-induced phenotypes were similar in B6 and B6.Sle123 mice; however, B6.Sle123 mice uniquely exhibited increased B1 and plasma cells after IFN-a exposure, although both strains had an overall loss of mature B cells in the bone marrow, spleen and periphery. Although most of the cellular effects of IFN-a were identical in both strains, severe glomerulonephritis occurred only in B6.Sle123 mice. Mice injected with IFN-ADV showed an increase in immune complex deposition in the kidney, together with an unexpected decrease in serum anti-nuclear antibody levels. In summary, the predominant impact of systemic IFN-a in this murine model is an exacerbation of mechanisms mediating end organ damage.
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