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

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.