Characterizing surface costimulatory molecule expression on plasmacytoid dendritic cells in male and female B6.Nba2 lupus-prone mice.

Abstract

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disorder that primarily affects women and is characterized by the production of autoreactive antinuclear autoantibodies and elevated levels of serum interferon-alpha (IFN-α). Female B6 mice congenic for the Nba2 lupus susceptibility interval develop a lupus-like disease including antinuclear autoantibodies, glomerulonephritis, and elevated serum IFN-α. Plasmacytoid dendritic cells (pDC) are capable of secreting high amounts of IFN-α and also present antigen. Ablation of Siglec H+ plasmacytoid dendritic cells in female B6.Nba2 mice is sufficient to reduce serum IFN-α and prevent the production of antinuclear autoantibodies as well as the development of glomerulonephritis. We hypothesized that genetic and/or sex-specific differences in pDC activation states may contribute to differential susceptibility to lupus. Therefore, we compared the expression levels of specific costimulatory molecules on pDCs in male and female control (B6) and lupus-prone (B6.Nba2) mice. Plasmacytoid DCs were categorized into 3 subsets: Siglec H+ CD19−, CD19+ Siglec H−, or double negative. Using flow cytometry, the expression of CD80, CD86, CD40, CD40L, ICOS, B7RP1, and MHC Class II were quantified in each subset. This study may provide insights into the genetic and sex-specific mechanisms by which pDCs contribute to SLE pathogenesis.