Fairhurst Anna-Marie, Mathian Alexis, Connolly John E, Wang Andrew, Gray Hillery F, George Tiffany A, Boudreaux Christopher D, Zhou Xin J, Li Quan-Zhen, Koutouzov Sophie, Banchereau Jacques, Wakeland Edward K
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Eur J Immunol. 2008 Jul;38(7):1948-60. doi: 10.1002/eji.200837925.
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-alpha 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-alpha 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-alpha 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-alpha in this murine model is an exacerbation of mechanisms mediating end organ damage.
通过使用含有重组干扰素-α基因盒的腺病毒（ADV）表达载体（IFN-ADV），比较狼疮易感B6.Sle1Sle2Sle3（B6.Sle123）品系和其亲代C57BL/6（B6）同基因对照的表型变化，评估干扰素-α分泌对疾病进展的影响。对年轻B6和B6.Sle123小鼠的细胞谱系组成和活化进行全面比较，发现在存在和不存在全身性干扰素-α的情况下存在多种细胞改变。大多数干扰素-α诱导的表型在B6和B6.Sle123小鼠中相似；然而，B6.Sle123小鼠在接触干扰素-α后独特地表现出B1细胞和浆细胞增加，尽管两个品系在骨髓、脾脏和外周血中成熟B细胞总体上均减少。虽然干扰素-α的大多数细胞效应在两个品系中相同，但严重的肾小球肾炎仅发生在B6.Sle123小鼠中。注射IFN-ADV的小鼠肾脏中免疫复合物沉积增加，同时血清抗核抗体水平意外降低。总之，在该小鼠模型中全身性干扰素-α的主要影响是介导终末器官损伤的机制加剧。
