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Type I interferon signaling is involved in the spontaneous development of lupus-like disease in B6.Nba2 and (B6.Nba2 × NZW)F1 mice

Genes & Immunity volume 8, pages 653–662 (2007)Cite this article

Abstract

Several studies have described a role for type I interferons (IFNαβ) in the initiation and/or prolongation of autoimmune diseases. Most pronounced has been the association of disease activity with what is now known as ‘the interferon signature’ of gene expression in peripheral blood mononuclear cells from lupus patients. In correlation, studies have shown that inhibition of IFNαβ signaling abrogates disease in various mouse models of lupus. New Zealand black (NZB) and B6.Nba2 congenic mice spontaneously develop elevated levels of serum anti-nuclear autoantibodies (ANAs). Nevertheless, neither of these strains develop fatal renal disease. The female F1 offspring of NZB or B6.Nba2 crossed with New Zealand white (NZW) mice do, however, develop kidney disease. We have previously shown that increases in endogenous IFNαβ levels in (B6.Nba2 × NZW)F1 mice leads to accelerated development of renal disease in an IFNαβ-dependent manner. We now show that B6.Nba2 and (B6.Nba2 × NZW)F1 mice deficient for the IFNαβ-receptor fail to develop ANA and renal disease, although the mice have substantial immune complex deposition in the glomeruli. Thus, endogenous IFNαβ might influence disease by affecting B-cell activation and differentiation, as well as the kidneys’ susceptibility to damage, the latter perhaps through induction of a local inflammatory milieu.

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Acknowledgements

This study was funded by The Denver Autoimmunity Center of Excellence (#AI46374-07) (TNJ, PM, BLK).

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Author notes

  1. B L Kotzin: Amgen Inc., Thousand Oaks, CA, USA.

Authors and Affiliations

  1. Division of Clinical Immunology, University of Colorado Denver and Health Sciences Center, Denver, CO, USA

    T N Jørgensen, E Roper & B L Kotzin

  2. Division of Rheumatology, University of Colorado Denver and Health Sciences Center, Denver, CO, USA

    J M Thurman

  3. Integrated Department of Immunology, University of Colorado Denver and Health Sciences Center, Denver, CO, USA

    J M Thurman, P Marrack & B L Kotzin

  4. Howard Hughes Medical Institute and National Jewish Medical and Research Center, Denver, CO, USA

    P Marrack

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  1. T N Jørgensen
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Correspondence to T N Jørgensen.

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Jørgensen, T., Roper, E., Thurman, J. et al. Type I interferon signaling is involved in the spontaneous development of lupus-like disease in B6.Nba2 and (B6.Nba2 × NZW)F1 mice. Genes Immun 8, 653–662 (2007). https://doi.org/10.1038/sj.gene.6364430

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