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

J Immunol. 2008 Apr 1;180(7):5101-8. doi: 10.4049/jimmunol.180.7.5101.

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 Ly6C(high) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / immunology
  • Antigens, Ly / metabolism
  • Autoantibodies / biosynthesis
  • Autoantibodies / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Interferon Type I / biosynthesis*
  • Interferon Type I / classification
  • Interferon Type I / genetics
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / metabolism*
  • Lupus Erythematosus, Systemic / pathology*
  • Mice
  • Monocytes / immunology
  • Monocytes / metabolism
  • Terpenes / pharmacology

Substances

  • Antigens, Ly
  • Autoantibodies
  • Interferon Type I
  • Ly6 protein, mouse
  • Terpenes
  • pristane