Dendritic cells (DCs) have become steadily recognized as attractive drug targets due to their unique position in the immune system as initiators of primary immune responses. Their function and immunological properties are regulated by a myriad of proteins, which themselves are regulated by post-translational modifications (PTMs). Among these, O‑GlcNAcylation of intracellular proteins has been found to govern the activity of various proteins in immune cells. Although O-GlcNAcylation is highly conserved among all metazoans that have been studied so far, little is known about the regulatory mechanisms behind this PTM.
Our research focuses on investigating O-GlcNAcylation in dendritic cells, where this modification has not been described yet. In particular, we study how the O‑GlcNAc cycling enzymes O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA) are regulated in DCs as well as their functional implications.
We propose that OGT and OGA are integral players in DCs linking cell metabolism to their immunological functions. To examine this hypothesis, we are characterising these two enzymes biochemically and immunologically in a mouse dendritic cell line. We will provide evidence that the action of OGT and OGA affects intracellular proteins in steady state as well activated dendritic cells representing potential targets for the manipulation of immune responses for therapeutic purposes.