Immune synapse instructs epigenomic and transcriptomic functional reprogramming in dendritic cells

Understanding the fate of dendritic cells (DCs) after productive immune synapses (postsynaptic DCs) with T cells during antigen presentation has been largely neglected in favor of deciphering the nuances of T-cell activation and memory generation. Here, we describe that postsynaptic DC switch their transcriptomic signature, correlating with epigenomic changes including DNA accessibility and histone methylation. We focus on the chemokine receptor Ccr7 as a proof of concept gene that is increased in postsynaptic DCs. Consistent with our epigenomic observations, post-synaptic DCs migrate more efficiently towards CCL19 in vitro and display enhanced homing to draining lymph nodes in vivo. This work describes a new DC population whose transcriptomics, epigenomics and migratory capacity change in response to their cognate contact with T cells. We performed RNA and ATAC sequencing using CD11c+ MHCIIhigh dendritic cells incubated with LPS and pulsed (psDCs) or not (nsDCs) with the peptide OVA323-339 and then cocultured with CD4+ OT-II T cells for 24h.