A novel type i IFN-producing cell subset in murine lupus

Pui Y. Lee, Jason S. Weinstein, Dina C. Nacionales, Philip O. Scumpia, Yi Li, Edward Butfiloski, Nico Van Rooijen, Lyle Moldawer, Minoru Satoh, Westley H. Reeves

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Excess type I IFNs (IFN-I) have been linked to the pathogenesis of systemic lupus erythematosus (SLE). Therapeutic use of IFN-I can trigger the onset of SLE and most lupus patients display up-regulation of a group of IFN-stimulated genes (ISGs). Although this "IFN signature" has been linked with disease activity, kidney involvement, and autoantibody production, the source of IFN-I production in SLE remains unclear. 2,6,10,14-Tetramethylpentadecane- induced lupus is at present the only model of SLE associated with excess IFN-I production and ISG expression. In this study, we demonstrate that tetramethylpentadecane treatment induces an accumulation of immature Ly6C high monocytes, which are a major source of IFN-I in this lupus model. Importantly, they were distinct from IFN-producing dendritic cells (DCs). The expression of IFN-I and ISGs was rapidly abolished by monocyte depletion whereas systemic ablation of DCs had little effect. In addition, there was a striking correlation between the numbers of Ly6Chigh monocytes and the production of lupus autoantibodies. Therefore, immature monocytes rather than DCs appear to be the primary source of IFN-I in this model of IFN-I-dependent lupus.

Original languageEnglish (US)
Pages (from-to)5101-5108
Number of pages8
JournalJournal of Immunology
Volume180
Issue number7
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Lee, P. Y., Weinstein, J. S., Nacionales, D. C., Scumpia, P. O., Li, Y., Butfiloski, E., Van Rooijen, N., Moldawer, L., Satoh, M., & Reeves, W. H. (2008). A novel type i IFN-producing cell subset in murine lupus. Journal of Immunology, 180(7), 5101-5108. https://doi.org/10.4049/jimmunol.180.7.5101