CD8+XCR1neg Dendritic Cells Express High Levels of Toll-Like Receptor 5 and a Unique Complement of Endocytic Receptors

Abstract

Conventional dendritic cells (cDC) resident in the lymphoid organs of mice have been classically divided into CD8+ and CD8neg 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, CD8neg DCs are grouped together in the heterogeneous cDC2 subset. CD8neg 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+XCR1neg DCs have a gene expression profile that is consistent with both plasmacytoid DCs (pDCs) and cDC2. Our data demonstrate that CD8+XCR1neg 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.

Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines

“…In contrast to MHC-class-II mediated presentation to CD4+ T-cells, cross-presentation of VLP-derived antigens to CD8+ T-cells is usually restricted to a subset of CD8+ DCs [33]. However, this CD8+ DC subset that has the ability to cross-present [34] demonstrates the lowest level of relative TLR5 expression in comparison to the other conventional DCs [35]. This implies the need for comprehensive studies on the cross-presentation of flagellin-functionalized VLPs by different DC subsets.…”

Absence of Batf3 reveals a new dimension of cell state heterogeneity within conventional dendritic cells

“…DC cell states combining lineage features of cDC1, cDC2, and pDCs have been described by others. Wylie et al recently identified a CD8+XCR1À DC population, which expressed lineage-mixed gene signatures of pDCs, cDC1, and cDC2 (Wylie et al, 2018). They showed that these CD8+XCR1À DCs preferentially expressed TLR5 and TLR7, and a unique set of endocytic receptors, and their ability to induce T helper cell proliferation was comparable with cDC2.…”

IFNβ Is a Potent Adjuvant for Cancer Vaccination Strategies

“…Type I IFNs can act on CD8α + DCs to promote maturation and cross-priming ( 17 – 21 ). These DCs broadly comprise the cross-presenting DC subset (specifically the XCR1 + DC population ( 42 , 43 , 64 )) and have been shown to be crucial in mediating effective anti-tumor responses ( 65 ). Here we establish that cross-presenting XCR1 + DCs are essential for enhanced priming of tumor-specific CD8 + T cells during vaccination with IFNβ.…”