The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cells

TLDR

Human BDCA3+ dendritic cells are proposed homologues of mouse CD8α+ DCs, yet no shared marker had been identified and the chemokine ligand XCL1 is selectively expressed in NK and CD8+ T cells. The study aims to demonstrate that XCR1 is a conserved, specific marker for CD8α+ DC–like subsets in higher vertebrates and to evaluate its role in early CD8+ T‑cell defense against intracellular pathogens. Human BDCA3+ DCs cross‑present antigens and activate CD8+ T cells more efficiently than BDCA1+ or plasmacytoid DCs, mirroring mouse CD8α+ DCs; XCR1 is specifically expressed on these DCs across species, its ligand XCL1 is enriched in memory CD8+ T cells, and XCR1‑deficient mice exhibit impaired early CD8+ T‑cell responses and higher bacterial loads following Listeria monocytogenes infection.

Abstract

Human BDCA3+ dendritic cells (DCs) were suggested to be homologous to mouse CD8α+ DCs. We demonstrate that human BDCA3+ DCs are more efficient than their BDCA1+ counterparts or plasmacytoid DCs (pDCs) in cross-presenting antigen and activating CD8+ T cells, which is similar to mouse CD8α+ DCs as compared with CD11b+ DCs or pDCs, although with more moderate differences between human DC subsets. Yet, no specific marker was known to be shared between homologous DC subsets across species. We found that XC chemokine receptor 1 (XCR1) is specifically expressed and active in mouse CD8α+, human BDCA3+, and sheep CD26+ DCs and is conserved across species. The mRNA encoding the XCR1 ligand chemokine (C motif) ligand 1 (XCL1) is selectively expressed in natural killer (NK) and CD8+ T lymphocytes at steady-state and is enhanced upon activation. Moreover, the Xcl1 mRNA is selectively expressed at high levels in central memory compared with naive CD8+ T lymphocytes. Finally, XCR1−/− mice have decreased early CD8+ T cell responses to Listeria monocytogenes infection, which is associated with higher bacterial loads early in infection. Therefore, XCR1 constitutes the first conserved specific marker for cell subsets homologous to mouse CD8α+ DCs in higher vertebrates and promotes their ability to activate early CD8+ T cell defenses against an intracellular pathogenic bacteria.