Natural killer cells and dendritic epidermal γδ T cells orchestrate type 1 conventional DC spatiotemporal repositioning toward CD8+ T cells

Successful immune responses rely on a regulated delivery of the right signals to the right cells at the right time. Here we show that natural killer (NK) and dendritic epidermal gamma delta T cells (DETCs) use similar mechanisms to spatiotemporally orchestrate conventional type 1 dendritic cell (cDC1) functions in the spleen, skin, and its draining lymph nodes (dLNs). Upon MCMV infection in the spleen, cDC1 clusterize with activated NK cells in marginal zones. This XCR1-dependent repositioning of cDC1 toward NK cells allows contact delivery of IL-12 and IL-15/ IL-15R alpha by cDC1, which is critical for NK cell responses. NK cells deliver granulocyte-macrophage colony- stimulating factor (GM-CSF) to cDC1, guiding their CCR7-dependent relocalization into the T cell zone. In MCMV-infected skin, XCL1-secreting DETCs promote cDC1 migration from the skin to the dLNs. This XCR1-dependent licensing of cDC1 both in the spleen and skin accelerates antiviral CD8(+) T cell responses, revealing an additional mechanism through which cDC1 bridge innate and adaptive immunity.

Automated summary

Successful immune responses require the right signals to be delivered to the right cells at the right time. In the spleen and skin, NK cells and DETCs interact with cDC1 to accelerate antiviral CD8(+) T cell responses, bridging innate and adaptive immunity through additional mechanisms.