Transcriptional and Functional Analysis of CD1c(+) Human Dendritic Cells Identifies a CD163(+) Subset Priming CD8(+)CD103(+) T Cells

Bourdely, Pierre; Anselmi, Giorgio; Vaivode, Kristine; Ramos, Rodrigo Nalio; Missolo-Koussou, Yoann; Hidalgo, Sofia; Tosselo, Jimena; Nunez, Nicolas; Richer, Wilfrid; Vincent-Salomon, Anne; Saxena, Alka; Wood, Kristie; LLadser, Alvaro; Piaggio, Eliane; Helft, Julie; et. al.

Abstract

Dendritic cells (DCs) are antigen-presenting cells controlling T cell activation. In humans, the diversity, ontogeny, and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88(-)CD1c(+)CD163(+) DCs (called DC3s) as immediate precursors of inflammatory CD88(-)CD14(+)CD1c(+) CD163(+)Fc epsilon RI+ DCs. DC3s develop via a specific pathway activated by GM-CSF, independent of cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors. Like classical DCs but unlike monocytes, DC3s drove activation of naive T cells. In vitro, DC3s displayed a distinctive ability to prime CD8(+) T cells expressing a tissue homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor beta (TGF-beta) signaling. In vivo, DC3s infiltrated luminal breast cancer primary tumors, and DC3 infiltration correlated positively with CD8(+)CD103(+)CD69(+) tissue-resident memory T cells. Together, these findings define DC3s as a lineage of inflammatory DCs endowed with a strong potential to regulate tumor immunity.

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Título según WOS: ID WOS:000561190600013 Not found in local WOS DB
Título de la Revista: IMMUNITY
Volumen: 53
Número: 2
Editorial: Cell Press
Fecha de publicación: 2020
Página de inicio: 335
Página final: +
DOI:

10.1016/j.immuni.2020.06.002

Notas: ISI