Critical roles of a dendritic cell subset expressing a chemokine receptor, XCR1.

Dendritic cells (DCs) consist of various subsets that play crucial roles in linking innate and adaptive immunity. In the murine spleen, CD8 alpha(+) DCs exhibit a propensity to ingest dying/dead cells, produce proinflammatory cytokines, and cross-present Ags to generate CD8(+) T cell responses. To track and ablate CD8 alpha(+) DCs in vivo, we generated XCR1-venus and XCR1-DTRvenus mice, in which genes for a fluorescent protein, venus, and a fusion protein consisting of diphtheria toxin receptor and venus were knocked into the gene locus of a chemokine receptor, XCR1, which is highly expressed in CD8 alpha(+) DCs. In both mice, venus(+) cells were detected in the majority of CD8 alpha(+) DCs, but they were not detected in any other cells, including splenic macrophages. Venus(+) CD8 alpha(+) DCs were superior to venus 2 CD8 alpha(+) DCs with regard to their cytokine-producing ability in response to TLR stimuli. In other tissues, venus(+) cells were found primarily in lymph node (LN)-resident CD8 alpha(+), LN migratory and peripheral CD103(+) DCs, which are closely related to splenic CD8 alpha(+) DCs, although some thymic CD8 alpha(-)CD11b(-) and LN CD103(-) CD11b(-) DCs were also venus(+). In response to dsRNAs, diphtheria toxin-treated XCR1-DTR mice showed impaired CD8(+) T cell responses, with retained cytokine and augmented CD4(+) T cell responses. Furthermore, Listeria monocytogenes infection and anti-L. monocytogenes CD8(+) T cell responses were defective in diphtheria toxin-treated XCR1-DTRvenus mice. Thus, XCR1-expressing DCs were required for dsRNA-or bacteria-induced CD8(+) T cell responses. XCR1-venus and XCR1-DTRvenus mice should be useful for elucidating the functions and behavior of XCR1-expressing DCs, including CD8 alpha(+) and CD103(+) DCs, in lymphoid and peripheral tissues.