A STATus report on DC development

DCs have a vital role in the immune system by recognizing exogenous or self-antigens and eliciting appropriate stimulatory or tolerogenic adaptive immune responses. DCs also contribute to human autoimmune disease and, when depleted, to immunodeficiency. Moreover, DCs are being explored for potential use in clinical therapies including cancer treatment. Thus, understanding the molecular mechanisms that regulate DCs is crucial to improving treatments for human immune disease and cancer. DCs constitute a heterogeneous population including plasmacytoid (pDC) and classic (cDC) subsets; however, the majority of DCs residing in lymphoid organs and peripheral tissues in steady state share common progenitor populations, originating with hematopoietic stem cells. Like other hematopoietic lineages, DCs require extracellular factors including cytokines, as well as intrinsic transcription factors, to control lineage specification, commitment, and maturation. Here, we review recent findings on the roles for cytokines and cytokine-activated STAT transcription factors in DC subset development. We also discuss how cytokines and STATs intersect with lineage-regulatory transcription factors and how insight into the molecular basis of human disease has revealed transcriptional regulators of DCs. Whereas this is an emerging area with much work remaining, we anticipate that knowledge gained by delineating cytokine and transcription factor mechanisms will enable a better understanding of DC subset diversity, and the potential to manipulate these important immune cells for human benefit. J. Leukoc. Biol. 92: 445-459; 2012.