Systemic IFN-α drives kidney nephritis in B6.Sle123 mice

Anna Marie Fairhurst, Alexis Mathian, John E. Connolly, Andrew Wang, Hillery F. Gray, Tiffany A. George, Christopher D. Boudreaux, Xin J. Zhou, Quan Zhen Li, Sophie Koutouzov, Jacques Banchereau, Edward K. Wakeland

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

The impact of IFN-α 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-α 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-α. Most IFN-α-induced phenotypes were similar in B6 and B6.Sle123 mice; however, B6.Sle123 mice uniquely exhibited increased B1 and plasma cells after IFN-α 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-α 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-α in this murine model is an exacerbation of mechanisms mediating end organ damage.

Original languageEnglish (US)
Pages (from-to)1948-1960
Number of pages13
JournalEuropean Journal of Immunology
Volume38
Issue number7
DOIs
StatePublished - Jul 2008

Keywords

  • Congenic
  • IFN
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Fairhurst, A. M., Mathian, A., Connolly, J. E., Wang, A., Gray, H. F., George, T. A., Boudreaux, C. D., Zhou, X. J., Li, Q. Z., Koutouzov, S., Banchereau, J., & Wakeland, E. K. (2008). Systemic IFN-α drives kidney nephritis in B6.Sle123 mice. European Journal of Immunology, 38(7), 1948-1960. https://doi.org/10.1002/eji.200837925