Modulators of Dendritic Cells and B cells in Lupus

Abstract

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies directed against ubiquitous self-antigens, many of which are nuclear autoantigens like dsDNA and chromatin (Pisetsky, 2016), and by elevated type I interferons (IFN) (Hooks et al., 1979; Weckerle et al., 2011), a family of pro-inflammatory cytokines that have antiviral activity (Pestka et al., 2004). Microarray analysis of peripheral blood mononuclear cells (PBMC) from SLE patients discovered the increased expression of IFN-responsive genes that was named the IFN Signature (Baechler et al., 2003a; Bennett et al., 2003b; Crow et al., 2003). Genome wide association studies indicate a clear genetic component in lupus pathogenesis (Chung et al., 2011; SLEGEN et al., 2008) and murine models of SLE confirm genetic drivers of the disease (Morel, 2010; Morel et al., 2000). However, the concordance of SLE in monozygotic twins is only 30-40% (Connolly and Hakonarson, 2012), while the inc