Mechanisms of peripheral tolerance

Silvia Gregori

Silvia Gregori

Location: DIBIT1 A2, Floor 2, Room 13

Group leader, Mechanisms of peripheral tolerance Unit
Manager & Scientific Supervisor, Immune Core

During her early career, Dr. Gregori made pioneer work in studying the role of vitamin D3 and its analogues in transplantation tolerance and in preventing autoimmune diabetes, working in the group of Prof. L. Adorini. Moreover, she demonstrated, for the first time, that the pathogenesis of type 1 diabetes in NOD mice correlated with an enhanced pathogenicity of T effector cells and a decreased suppressive activity of regulatory T cells. Later, she elucidated new mechanisms of suppression mediated by T regulatory type 1 (Tr1) cells and identified DC-10 as major subset of dendritic cells involved in Tr1 cell differentiation working in the group of Prof. Maria Grazia Roncarolo. These studies have been instrumental to the definition of a protocol for the induction of Tr1 cells for cell therapy. She also contributed to the definition of a new protocol for Tr1 cell induction using IL-10 gene transfer and in the discovery of the specific biomarkers of Tr1 cells and DC-10.

As an independent researcher Dr. Gregori focused her research on tolerogenic dendritic cells (tolDCs), their role in modulating immune responses, and their use as a therapy to prevent/control adverse immune responses. Advances in cell manufacturing technologies allowed evaluation of tolDCs in proof-of-principle clinical trials, showing the feasibility and safety of the approach. However, the mainstream use of tolDCs is challenged by the current lack of methods to efficiently generate stable and effective tolerogenic cells from patients with concurrent inflammatory/metabolic dysregulation. To this end, Dr. Gregori is currently unveiling the fitness of tolDC precursors in healthy and pathological conditions for optimal in vitro differentiation of tolDCs, identifying novel molecular targets promoting effective tolDC generation, defining the role of IL-10-producing DC (DC-10) in promoting and maintaining immunological tolerance. Moreover, she is actively involved in dissecting the impact of pre-existing immunity on protein replacement therapy and on gene therapy, and how to tackle the potential adverse immune responses using tolDCs.