Human dendritic cell subsets

Abstract

Dendritic cells are highly adapted to their role of presenting antigen and directing immune responses. Developmental studies indicate that DCs originate independently from monocytes and tissue macrophages. Emerging evidence also suggests that distinct subsets of DCs have intrinsic differences that lead to functional specialisation in the generation of immunity. Comparative studies are now allowing many of these properties to be more fully understood in the context of human immunology.

Keywords: dendritic cells; haematology; therapy/immunotherapy.

Figure 1

Transcriptional profiling of blood monocytes and dendritic cells (DCs). (a) Principal component analysis; (b) Connectivity mapping (cMAP) of gene set enrichment. The prinicipal components (PCs) are vectors that account for most of the variability in the populations and illustrate the clustering of all monocyte populations separately from DCs. Plasmacytoid DCs have the most distinct DC signature and cluster away from the two myeloid DCs and the monocyte cluster. The percentage variation accounted for by PC1 and PC2 in the example shown is 32·6% and 13·7%, respectively. Connectivity mapping defines the enrichment of different populations for a given gene signature. The cMAP enrichment score is a scalar quantity normalized to the index gene signature. The example shows the enrichment of monocyte and DC transcriptional profiles for the CD14 monocyte signature, illustrating the relatedness of all monocyte populations, intermediate status of CD1c⁺ DCs and distant relationship of CD141⁺ DCs and pDCs. The gene signature of each population is defined by those genes whose expression exceeds an average obtained from all the other populations. Each point represents a biological replicate (n = 6). Data replotted from ref. courtesy of Pavandip Wasan, Michael Poidinger and Florent Ginhoux (Singapore Immunology Network).

Figure 2

The distribution of major human dendritic cell (DC) subsets in blood, epithelial tissues and lymph nodes. Broken arrows indicate relationships that require further confirmation in humans. Human DCs can be generated either from granulocyte–macrophage progenitors (GMP) or multi-lymphoid progenitors (MLP) both of which ultimately arise from haematopoietic stem cells (HSC). Classical monocytes, blood myeloid DC (mDC) and plasmacytoid DC (pDC) are putative precursors of tissue and lymphoid DCs. Non-classical monocytes are reported to arise by conversion of classical monocytes in the mouse. Inflammatory DCs and CD14⁺ DCs have transcriptional profiles suggesting that they arise from monocytes; likewise tissue CD1c⁺ DCs and CD141⁺ DCs are related to their blood counterparts. Myeloid DCs and Langerhans cells (LCs) both form interdigitating cells in skin-draining lymph nodes. CD14⁺ DCs and pDCS are also found in nodes but may arise directly from the blood rather than by migration from tissues.