title: Animal Models of Interferon Signature Positive Lupus.
abstract: Human lupus is strongly associated with a gene expression signature characterized by over-expression of Type I interferon-regulated genes. A strong interferon signature generally is not seen in the standard mouse models of lupus, despite considerable evidence for the involvement of toll-like receptor-driven interferon production. In contrast, pristane-induced lupus exhibits a prominent TLR7-dependent interferon signature. Importantly, genetic disorders with dysregulated interferon production in both human beings and mice cause severe autoinflammatory diseases but not the typical manifestations of lupus, suggesting that interferon over-production is insufficient to cause systemic lupus erythematosus itself. Single-gene models in mice suggest that lupus-like disease may result from abnormalities in B-cell activation and the clearance of dead cells. Pristane may mimic human systemic lupus erythematosus by causing synergistic abnormalities in interferon production along with defective clearance of apoptotic cells and over-active B-cell signaling.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida , Gainesville, FL , USA.
authors.forename: Haoyang
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida , Gainesville, FL , USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Szeto
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida , Gainesville, FL , USA.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL , USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida , Gainesville, FL , USA.
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
keywords: B-cell activation; animal models; apoptosis; interferon alpha; lupus erythematosus; pristane; systemic; toll-like receptors