Type I and Type III interferons, major players in protective anti-viral responses and detrimental autoimmune interferonopathies, are major cytokines produced by dendritic cells.
Indeed, the production of interferons by dendritic cells, and their responses to them, are thought to critically drive dendritic cell function, enabling cross-priming and induction of cytotoxic T cell responses.
However, the mechanisms by which interferons regulate key dendritic cell functions are currently unknown. Our data indicates that whilst type I interferons drive thousands of interferon stimulated genes (ISGs) in dendritic cells, they also instigate a massive, rapid, post-translational series of events, with major kinases driving phosphorylation and activation of pathways not classically viewed as interferon-driven.
On the other hand, type III interferon fails to induce robust transcriptional responses in dendritic cells, but also drives a robust regulation of pathways through phosphorylation and dephosphorylation events. There is some indication that key pathways are shared between type I and type III interferons, whereby they are negatively regulated by type III, put positively regulated by type I. Further, pathways known to actively inhibit type I interferon signalling are promoted by interferon-lambda.
Together our data, combining transcriptomics, phospho- and total proteomics and chromatin accessibility, sheds a new light on the regulation of dendritic cell functions by interferons.