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Migratory CD103 +  and lymphoid-resident CD8 +  dendritic cells (DCs) share many attributes, such as dependence on the same transcription factors, cross-presenting ability and expression of certain surface molecules, such that it has been proposed they belong to a common sub-lineage. The functional diversity of the two DC types is nevertheless incompletely understood. Here we reveal that upon skin infection with herpes simplex virus, migratory CD103 +  DCs from draining lymph nodes were more potent at inducing Th17 cytokine production by CD4 +  T cells than CD8 +  DCs. This superior capacity to drive Th17 responses was also evident in CD103 +  DCs from uninfected mice. Their differential potency to induce Th17 differentiation was reflected by higher production of IL-1β and IL-6 by CD103 +  DCs compared with CD8 +  DCs upon stimulation. The two types of DCs from isolated lymph nodes also differ in expression of certain pattern recognition receptors. Furthermore, elevated levels of GM-CSF, typical of those found in inflammation, substantially increased the pool size of CD103 +  DCs in lymph nodes and skin. We argue that varied levels of GM-CSF may explain the contrasting reports regarding the positive role of GM-CSF in regulating development of CD103 +  DCs. Together, we find that these two developmentally closely-related DC subsets display functional differences and that GM-CSF has differential effect on the two types of DCs.

The Closely Related CD103+ Dendritic Cells (DCs) and Lymphoid-Resident CD8+ DCs Differ in Their Inflammatory Functions