title: Deficiency of the type I interferon receptor protects mice from experimental lupus.
abstract: OBJECTIVE
  Systemic lupus erythematosus (SLE) is diagnosed according to a spectrum of clinical manifestations and autoantibodies associated with abnormal expression of type I interferon (IFN-I)-stimulated genes (ISGs). The role of IFN-I in the pathogenesis of SLE remains uncertain, partly due to the lack of suitable animal models. The objective of this study was to examine the role of IFN-I signaling in the pathogenesis of murine lupus induced by 2,6,10,14-tetramethylpentadecane (TMPD).
  
  
  METHODS
  IFN-I receptor-deficient (IFNAR(-/-)) 129Sv mice and wild-type (WT) 129Sv control mice were treated intraperitoneally with TMPD. The expression of ISGs was measured by real-time polymerase chain reaction. Autoantibody production was evaluated by immunofluorescence and enzyme-linked immunosorbent assay. Proteinuria and renal glomerular cellularity were measured and renal immune complexes were examined by immunofluorescence.
  
  
  RESULTS
  Increased ISG expression was observed in the peripheral blood of TMPD-treated WT mice, but not in the peripheral blood of TMPD-treated IFNAR(-/-) mice. TMPD did not induce lupus-specific autoantibodies (anti-RNP, anti-Sm, anti-double-stranded DNA) in IFNAR(-/-) mice, whereas 129Sv controls developed these specificities. Although glomerular immune complexes were present in IFNAR(-/-) mice, proteinuria and glomerular hypercellularity did not develop, whereas these features of glomerulonephritis were found in the TMPD-treated WT controls. The clinical and serologic manifestations observed in TMPD-treated mice were strongly dependent on IFNAR signaling, which is consistent with the association of increased expression of ISGs with lupus-specific autoantibodies and nephritis in humans.
  
  
  CONCLUSIONS
  Similar to its proposed role in human SLE, signaling via the IFNAR is central to the pathogenesis of autoantibodies and glomerulonephritis in TMPD-induced lupus. This lupus model is the first animal model shown to recapitulate the "interferon signature" in peripheral blood.
authors.affiliation: University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Kindra M
authors.initials: KM
authors.lastname: Kelly-Scumpia
authors.forename: Pui Y
authors.initials: PY
authors.lastname: Lee
authors.forename: Jason S
authors.initials: JS
authors.lastname: Weinstein
authors.forename: Robert
authors.initials: R
authors.lastname: Lyons
authors.forename: Eric
authors.initials: E
authors.lastname: Sobel
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000276:immunology; D007166:Immunosuppressive Agents; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D008181:Lupus Nephritis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D053633:Receptor, Interferon alpha-beta / Q000235:genetics*; D013729:Terpenes
chemical_list: D001323:Autoantibodies; C508032:Ifnar1 protein, mouse; D007166:Immunosuppressive Agents; D013729:Terpenes; D053633:Receptor, Interferon alpha-beta; C009042:pristane