Critical Roles of a Dendritic Cell Subset Expressing a Chemokine Receptor, XCR1

Abstract

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.

Development of a Novel CD4+ TCR Transgenic Line That Reveals a Dominant Role for CD8+ Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria

“…XCR1 is a chemokine receptor expressed by mature CD8 + DC and by their migratory CD103 + counterparts, found in LN. DT treatment of XCR1-DTRvenus mice, which express the DT receptor under the XCR1 promoter, results in the elimination of CD8 + DC from the spleen (46). Consistent with the results obtained using IRF8-deficient mice infected with bloodstage PbA, PbT-II proliferation was significantly reduced in the spleen of DT-treated XCR1-DTRvenus mice, amounting to ∼30% of WT controls (Fig.…”

Systemic DC Activation Modulates the Tumor Microenvironment and Shapes the Long-Lived Tumor-Specific Memory Mediated by CD8+ T Cells

“…S3B). XCR1 þ DCs is the relevant of CD8a þ subset of CD11c þ splenic DCs and are responsible for cross-presentation of exogenous antigen (22). We confirmed that XCR1 is exclusively expressed among CD8a Fig.…”

“…Ly5.1 mice and screening for the presence of Va2 and Ly5.1 and absence of Ly5.2 by flow cytometry. OT-1 TCR transgenic mice, CD11c-DTR/GFP mice (21), and XCR1-DTR-venus mice (22) and other all the mice were maintained under specific pathogen-free conditions and studied in compliance with our institutional guidelines.…”

Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node

“…multicolor histological images suggested that these cross-presenting DC subsets were preferentially accumulated in deep areas of the T-cell zone in the SDLNs (12). Other studies directly visualized both DC subsets by histological analyses of chemokine (C motif) receptor 1 (XCR1) expression, which is selectively and highly expressed in both LN-resident DCs and migratory DCs (13)(14)(15)(16) + T-cell activation.…”