CD8 + XCR1 neg Dendritic Cells Express High Levels of Toll-Like Receptor 5 and a Unique Complement of Endocytic Receptors.

Conventional dendritic cells (cDC) resident in the lymphoid organs of mice have been classically divided into CD8 ⁺ and CD8 ^neg subsets. It is well-established that CD8 ⁺ dendritic cells (DCs) and their migratory counterparts in the periphery comprise the cross-presenting cDC1 subset. In contrast, CD8 ^neg DCs are grouped together in the heterogeneous cDC2 subset. CD8 ^neg DCs are relatively poor cross-presenters and drive more prominent CD4 ⁺ T cell responses against exogenous antigens. The discovery of the X-C motif chemokine receptor 1 (XCR1) as a specific marker of cross-presenting DCs, has led to the identification of a divergent subset of CD8 ⁺ DCs that lacks the ability to cross-present. Here, we report that these poorly characterized CD8 ⁺ XCR1 ^neg DCs have a gene expression profile that is consistent with both plasmacytoid DCs (pDCs) and cDC2. Our data demonstrate that CD8 ⁺ XCR1 ^neg DCs possess a unique pattern of endocytic receptors and a restricted toll-like receptor (TLR) profile that is particularly enriched for TLR5, giving them a unique position within the DC immunosurveillance network.