Pro- and Anti-inflammatory Neutrophils in Lupus

A hallmark of SLE is the presence of elevated levels of circulating anti-nuclear autoantibodies specific towards chromatin, histones or dsDNA. Understanding the regulation of antibody production is therefore of utmost importance in understanding lupus pathogenesis. Spearheaded by the identification of accumulating immunosuppressive neutrophils in cancer patients, the nature and function of neutrophils have expanded from a uniform pro-inflammatory cell population to a heterogeneous population of cells with pro-inflammatory or immunosuppressive capacities. While much is known about pro-inflammatory neutrophils and the likely pathogenic function of such cells in lupus, a potential role for immunosuppressive neutrophils in protecting genetically predisposed individuals has only recently emerged. For example, SLE-derived neutrophils spontaneously produce type I interferons (IFNα), strongly associated with disease development, release chromatin-containing neutrophil extracellular traps (NETs), potentially functioning as a source of nuclear auto-antigen, and may activate B cells in a T cell independent fashion. In contrast, levels and functions of regulatory neutrophils (Nregs) involved in T celldependent B cell differentiation and germinal center reactions, are dysregulated in female lupus-prone mice during disease development. Here we review data supporting a role for both pro- and anti-inflammatory neutrophils in lupus.