Type I interferon (IFN) is a family of 15 cytokines (in human 13, 1,1) which exert several cellular functions through the binding to a common receptor. Despite the initial activation of the same Jak/Stat signalling pathway, the cellular response may be different depending on the type I IFN subtype. We investigated the activity of different type I IFN subtypes - IFN1, 2, 8, 21, and - on the differentiation of DC. Transcriptome analyses identified two distinct groups, the IFN/-DC and the IFN-DC. 78 genes, 7 chemokines and expression levels of cell surface markers characteristic of DC distinguished IFN-DC and IFN-DC. These differences are unlikely to impact the efficacy of T cell functional response since IFN2-DC and IFN-DC were equipotent in inducing the proliferation and the polarization of allogenic nave CD4 T cells into Th1 cells and in stimulating autologous memory CD4 or CD8 T cells. In contrast, IFN2-DC were found to be more efficient than IFN-DC in the phagocytic uptake of dead cells.