Type I interferons drive the maturation of human DC3s with a distinct costimulatory profile characterized by high GITRL
Mélanie Girard, Jaclyn C. Law, Maria I. Edilova, Tania H. Watts
Abstract
monocytes, characterized by high expression of MHCII, Fc receptors, and components of the phagocyte NADPH oxidase. IFN-β induced a shared core response in human DC and monocyte subsets as well as subset-specific responses, including differential expression of costimulatory molecules. Gene regulatory network analysis suggests that upon IFN-β stimulation NFKB1 drives DC3s to acquire a maturation program shared with DC2s. Accordingly, inhibition of NF-κB activation prevented the acquisition of a mature phenotype by DC3s upon IFN-β exposure. Collectively, this study provides insight into the cell type-specific response of human DC and monocyte subsets to IFN-I and highlights the distinct costimulatory potential of DC3s.