PDL1 AND ICOSL DISCRIMINATE HUMAN SECRETORY AND HELPER DENDRITIC CELLS

Dendritic cells (DC) are described as immature at the steady state, with a high antigen capture capacity, turning into a mature state with a strong T cell stimulatory capacity upon activation. Using 16 different stimuli in vitro (130 observations), we describe two states of human activated dendritic cells. PDL1highICOSLlow 9secretory DC9 produced large amounts of inflammatory cytokines and chemokines but induced very low levels of T helper (Th) cytokines following DC-T co-culture; conversely PDL1lowICOSLhigh 9helper DC9 produced low levels of secreted factors but induced high levels of Th cytokines characteristic of a broad range of Th subsets. Secretory DC were phenotypically identified in T cell inflamed primary head and neck squamous cell carcinoma. RNAseq analysis showed that they expressed a typical secretory DC signature, including CD40, PVR, IL1B, TNF, and CCL19. This novel and universal functional dichotomy of human DC opens broad perspectives for the characterization of inflammatory diseases, and for immunotherapy.