DNGR-ing the dendritic cell lineage.

Dendritic cells (DCs) are a group of functionally specialized antigensensing and antigen-presenting cells that initiate and orchestrate immunity. DCs are uniquely equipped to recognize pathogens, vaccines and self-antigens, and to instruct simultaneously the type, magnitude and specificity of immune responses. They are remarkably heterogeneous, and identifying different subsets on the basis of phenotypic and functional characteristics has proven challenging. In a recent issue of Cell, the Reis e Sousa group has overcome the existing limitations by developing the first true fate-mapping model of DC progenitors [1]. Distinct DC subsets have been traditionally identified by characteristic anatomical location, phenotype and function. The broadest division separates resident DCs in lymphoid tissue (LT) from nonlymphoid tissue (NLT) DCs that migrate to the lymph nodes through the lymphatics (Fig 1). In mice, resident LT DCs are often referred to as conventional DCs (cDCs), to distinguish them from migratory DCs and plasma cytoid DCs (pDCs), which produce vast amounts of interferon-α (IFN-α) during viral infection. cDCs are divided into two main subsets based on phenotype: CD8α+ DCs, CD4+CD11b+ DCs and a minor CD8α– CD4–CD11b+ DC subset [2]. More recently, high expression of endothelial cell-specific adhesion molecule (ESAM) was shown to characterize CD4+ splenic DCs [3]. Migratory DCs are generally distinguished by mutually exclusive surface expression of the integrins CD103 and CD11b, except in the lamina propria, in which an additional subset co-expressing CD103 and CD11b can be found [2]. Importantly, inflammation induces the generation of inflammatory DCs (iDCs) with additional phenotypic and functional characteristics. However, whether iDCs have a common origin with their steady-state counterparts, or arise through alternative differentiation pathways, is unclear. Analyses of the growth and transcription factor requirements of the different DC subsets have helped understand their interrelationships. CD103+ DCs and CD8α+ DCs are considered a distinct DC lineage, which is dependent on the Fmslike tyro sine kinase 3 ligand receptor (Flt3) and the transcription factors ID2, BATF3 and IRF8, and can efficiently cross-present antigens and stimulate CD8+ T-cell immunity [2]. DNGR-ing the dendritic cell lineage