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Bourdely, Pierre; Anselmi, Giorgio; Vaivode, Kristine; Ramos, Rodrigo Nalio; Missolo-Koussou, Yoann; Hidalgo, Sofia; Tosselo, Jimena; Nuñez, Nicolas; Richer, Wilfrid; Vincent-Salomon, Anne; Saxena, Alka; Wood, Kristie; Lladser, Alvaro; Piaggio, Eliane; Helft, Julie; Guermonprez, Pierre
Immunity (Cambridge, Mass.), 08/2020, Letnik: 53, Številka: 2Journal Article
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+FcεRI+ 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 β (TGF-β) 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. Display omitted •DC3s are phenotypic and functional intermediates between cDC2s and monocytes•GM-CSF alone, but not FLT3L, supports efficient differentiation of DC3s•DC3s do not differentiate via cDC (CDP)- or monocyte-restricted (cMoP) progenitors•DC3s prime TRM cells in vitro and correlate with TRM expansion in primary breast cancer Bourdely et al. identify human CD88−CD1c+CD163+ DC3s as a pro-inflammatory phagocyte lineage sharing features with monocytes and conventional DCs. DC3s efficiently induce differentiation of CD103+CD8+ T cells in vitro, and their infiltration correlates with CD8+CD69+CD103+ TRM accumulation in breast tumors.
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