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, CD8α⁺ 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 CD8α⁺ 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 CD8α⁺ DCs. In both mice, venus⁺ cells were detected in the majority of CD8α⁺ DCs, but they were not detected in any other cells, including splenic macrophages. Venus⁺CD8α⁺ DCs were superior to venus^-CD8α⁺ 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 CD8α⁺, LN migratory and peripheral CD103⁺ DCs, which are closely related to splenic CD8α⁺ DCs, although some thymic CD8α^-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 CD8α⁺ and CD103⁺ DCs, in lymphoid and peripheral tissues.