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

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.