A Pivotal Role for the Natural Interferon α–producing Cells (Plasmacytoid Dendritic Cells) in the Pathogenesis of Lupus

The human type I IFN gene family consists of 13 genes encoding IFN-α subtypes and one gene each for IFN-β and -ω. The type I IFN proteins show similarities with respect to both structure and function; for instance, they are typically produced by cells exposed to virus and interact with the same receptor, the IFNAR (1). The type I IFNs have well established direct antiviral and antiproliferative effects, but also several prominent immunoregulatory actions that have come into focus in recent years (1–3). The latter include the ability to promote survival and differentiation of antigen-activated Th1 cells. These effects of type I IFN may, in part, be due to their ability to activate signal transducer and activator of transcription (STAT)4 and maintain expression of a functional IL-12R. Type I IFN can also cause maturation of efficiently antigen-presenting monocyte-derived dendritic...