Novel strategies to generate tolerogenic DC for Ag-specific immunotherapy

The major goals of this research project are to generate stable and effective human tolerogenic dendritic cell (tolDC) suitable for cell-based approaches, to unravel the key molecular and cellular mechanisms controlling immune tolerance, and to identify novel targets controlling tolerogenic pathways. We focused our research on IL-10-secreting DC: our translational studies aim at developing innovative DC-based approaches, by means of exogenous IL-10 and/or lentiviral vector-mediated gene transfer, for the modulation of T-cell mediated diseases; our basic studies focused on IL-10 regulatory cells and in particular to a peculiar subset, named DC-10. We aim at defining the role of DC-10 in promoting/maintaining IL-10-mediated tolerance in healthy and pathological conditions. To better understand the molecular mechanisms underlying regulatory cell biology, we also aim at studying the epigenetic landscape of in vitro induced and ex vivo isolated regulatory cells.  
The success of our research project will help designing a safer tolDC-based cell therapy, abrogating the possibility to boost autoimmunity, and to stably preserve the tolerogenic properties of in vivo transferred DC, even in a pro-inflammatory environment. By identifying the genetic and epigenetic regulatory element controlling the tolerogenic properties of regulatory cells, we will also be able to develop new/better methods to produce tolerogenic cells for cell therapy to restore/induce tolerance to a specific Ag.