A novel type I IFN-producing cell subset in murine lupus.
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.
Lee
Pui Y
PY
Division of Rheumatology & Clinical Immunology and Center for Autoimmune Disease, University of Florida, Gainesville, FL 32610-0221, USA.
Weinstein
Jason S
JS
Nacionales
Dina C
DC
Scumpia
Philip O
PO
Li
Yi
Y
Butfiloski
Edward
E
van Rooijen
Nico
N
Moldawer
Lyle
L
Satoh
Minoru
M
Reeves
Westley H
WH
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology
D000950:Antigens, Ly; D001323:Autoantibodies; D007370:Interferon Type I; C526827:Ly6 protein, mouse; D013729:Terpenes; C009042:pristane