Interferon-α treatment of Female (NZW × BXSB)F 1 mice mimics some but not all features associated with the Yaa mutation

Meera Ramanujam, Philip Kahn, Weiqing Huang, Haiou Tao, Michael P. Madaio, Stephen M. Factor, Anne Davidson

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Objective. Male (NZW x BXSB)F 1 mice develop antiphospholipid syndrome (APS) and proliferative glomerulonephritis that is markedly accelerated by the Yaa locus encoding an extra copy of Tlr7. Female (NZW x BXSB)F 1 mice with only 1 active copy of Tlr7 develop late-onset glomerulonephritis but not APS. Because a major function of Toll-like receptor 7 is to induce type I interferons (IFNs), our goal was to determine whether IFNa can induce or accelerate the manifestations of systemic lupus erythematosus (SLE) in female (NZW x BXSBJFi mice. Methods. Eight-week-old female (NZW x BXSB)F1 mice were injected with a single dose of adenovirus expressing IFNα. Mice were monitored for the development of thrombocytopenia and proteinuria. Sera were tested for anticardiolipin and anti-Sm/RNP antibodies. Mice were killed at 17 or 22 weeks of age, and their kidneys and hearts were examined histologically and by immunohistochemistry. Spleen cells were phenotyped, and enzyme-linked immunospot assays for autoantibody-producing B cells were performed. Results. IFNα markedly accelerated nephritis and death in female (NZW X BXSB)F 1 mice. A significant increase in spleen cell numbers associated with a striking increase in the number of activated B and T cells was observed. Marginal-zone B cells were retained. IFNa-induced increased titers of autoantibodies were observed, but thrombocytopenia was not observed. Cardiac damage was milder than that in male mice. Conclusion. IFNa accelerates the development of renal inflammatory disease in female (NZW X BXSB)F 1 mice but induces only mild APS and does not induce thrombocytopenia. The effect of IFNα on SLE disease manifestations is strain dependent. These findings are relevant to our understanding of the physiologic significance of the IFN signature.

Original languageEnglish (US)
Pages (from-to)1096-1101
Number of pages6
JournalArthritis and Rheumatism
Volume60
Issue number4
DOIs
StatePublished - Apr 1 2009

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Interferons
Mutation
Antiphospholipid Syndrome
Thrombocytopenia
B-Lymphocytes
Therapeutics
Glomerulonephritis
Systemic Lupus Erythematosus
Autoantibodies
Spleen
Toll-Like Receptor 7
Kidney
neurotensin mimic 1
Enzyme-Linked Immunospot Assay
Interferon Type I
Nephritis
Proteinuria
Adenoviridae
Cell Count
Immunohistochemistry

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Ramanujam, M., Kahn, P., Huang, W., Tao, H., Madaio, M. P., Factor, S. M., & Davidson, A. (2009). Interferon-α treatment of Female (NZW × BXSB)F 1 mice mimics some but not all features associated with the Yaa mutation. Arthritis and Rheumatism, 60(4), 1096-1101. https://doi.org/10.1002/art.24414

Interferon-α treatment of Female (NZW × BXSB)F 1 mice mimics some but not all features associated with the Yaa mutation. / Ramanujam, Meera; Kahn, Philip; Huang, Weiqing; Tao, Haiou; Madaio, Michael P.; Factor, Stephen M.; Davidson, Anne.

In: Arthritis and Rheumatism, Vol. 60, No. 4, 01.04.2009, p. 1096-1101.

Research output: Contribution to journalArticle

Ramanujam, M, Kahn, P, Huang, W, Tao, H, Madaio, MP, Factor, SM & Davidson, A 2009, 'Interferon-α treatment of Female (NZW × BXSB)F 1 mice mimics some but not all features associated with the Yaa mutation', Arthritis and Rheumatism, vol. 60, no. 4, pp. 1096-1101. https://doi.org/10.1002/art.24414
Ramanujam, Meera ; Kahn, Philip ; Huang, Weiqing ; Tao, Haiou ; Madaio, Michael P. ; Factor, Stephen M. ; Davidson, Anne. / Interferon-α treatment of Female (NZW × BXSB)F 1 mice mimics some but not all features associated with the Yaa mutation. In: Arthritis and Rheumatism. 2009 ; Vol. 60, No. 4. pp. 1096-1101.
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