CD14(+) monocytes as dendritic cell precursors: Diverse maturation-inducing pathways lead to common activation of NF-kappa B/RelB

Dendritic cells are extremely potent antigen-presenting cells that are prim arily responsible for the sensitization of naive T cells to protein antigen in vivo. For this reason, dendritic cells are the focus of intense study. Despite this interest, relatively little information is available on the si gnal transduction pathways that regulate the development and activity of th ese cells. The last several years, however, have seen a steady accumulation of data regarding methods to cultivate large numbers of DC, the characteri zation of attendant signals that drive DC development from various precurso r cells, and the induction of nuclear transcription factors that presumably direct alterations in gene expression that regulate aspects of DC developm ent. In this review, we briefly summarize some of these findings, with emph asis on monocyte-derived dendritic cells and a discussion of two distinct t ypes of signaling pathways that appear to regulate the final maturation of DC: one pathway calcium-dependent and cyclosporine A-sensitive, the other p athway CsA-insensitive. Although evidence suggests these signaling pathways are quite divergent in their upstream components, they both appear to acti vate NF-kappaB nuclear factors, particularly RelB.