Deficiency of type I interferon contributes to Sle2-associated component lupus phenotypes

Jianwei Li, Yang Liu, Chun Xie, Jiankun Zhu, Desi Kreska, Laurence Morel, Chandra Mohan

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Abstract

Objective. Studies in mice and humans have implicated type I interferon (IFN-I) in the pathogenesis of lupus. Given that the locus for IFN-I is positioned within the Sle2 murine lupus susceptibility interval on chromosome 4, we undertook this study to investigate whether differences in IFN-I levels might potentially contribute to the phenotypes ascribed to this locus. Methods. IFN-I, anti-IFN-I, isotype control antibody, or phosphate buffered saline was administered to C57BL/6 and B6.Sle2 mice, and the serologic and cellular phenotypes were studied. In addition, B6.Sle2 mice were examined for structural and expression polymorphisms in the IFN-I gene. Results. In both B6.Sle2 congenic mice and C57BL/6 control mice, antibody-mediated blockade of IFN-I augmented serum autoantibody levels and boosted B1a cell numbers. Administration of IFN-I ameliorated these 2 features previously attributed to this disease locus. Importantly, compared with B6 controls, B6.Sle2 mice had reduced levels of IFN-I in their sera and cell culture supernatants, following stimulation. Although several sequence polymorphisms were noted in the Sle2 alleles of various IFN-I genes, it was not established whether any of the noted sequence variations were causally related to the observed phenotypes. Conclusion. Unexpectedly, reduction of IFN-I levels reproduced the serologic and cellular phenotypes previously associated with the Sle2 lupus susceptibility interval. Placing these findings in the context of other studies, the effect of IFN-I on systemic autoimmunity appears to be far more complex than originally perceived.

Original languageEnglish (US)
Pages (from-to)3063-3072
Number of pages10
JournalArthritis and rheumatism
Volume52
Issue number10
DOIs
StatePublished - Oct 1 2005

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ASJC Scopus subject areas

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

Cite this

Li, J., Liu, Y., Xie, C., Zhu, J., Kreska, D., Morel, L., & Mohan, C. (2005). Deficiency of type I interferon contributes to Sle2-associated component lupus phenotypes. Arthritis and rheumatism, 52(10), 3063-3072. https://doi.org/10.1002/art.21307