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

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.