Systemic IFN-alpha drives kidney nephritis in B6.Sle123 mice.
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.
Fairhurst
Anna-Marie
AM
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA. anna-marie.fairhurst@utsouthwestern.edu
Mathian
Alexis
A
Connolly
John E
JE
Wang
Andrew
A
Gray
Hillery F
HF
George
Tiffany A
TA
Boudreaux
Christopher D
CD
Zhou
Xin J
XJ
Li
Quan-Zhen
QZ
Koutouzov
Sophie
S
Banchereau
Jacques
J
Wakeland
Edward K
EK
D000818:Animals; D000936:Antigen-Antibody Complex; D001402:B-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005822:Genetic Vectors; D005921:Glomerulonephritis / Q000276:immunology* / Q000378:metabolism; D016898:Interferon-alpha / Q000276:immunology*; D007668:Kidney / Q000473:pathology; D007970:Leukopenia / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008181:Lupus Nephritis / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D013163:Splenomegaly / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000936:Antigen-Antibody Complex; D016898:Interferon-alpha