San Raffaele Telethon Institute for Gene Therapy

Mechanisms of peripheral tolerance


Group Leader

Silvia Gregori


Main interest of the Unit is to unravel the key molecular and cellular mechanisms controlling immune tolerance, responsible for maintaining tissue homeostasis and avoiding adverse immune responses. The Unit aims at studying and modulating antigen(Ag)-specific immune responses, to develop efficient therapeutic approaches to (re)establish Ag-specific immune tolerance in allogeneic bone marrow and solid organ transplantation, autoimmune diseases, allergy, and gene therapy. Together with the more studied regulatory T cells (Tr1 and CD25+FOXP3+ Treg), growing evidence indicates that different subsets of dendritic cells (DC), play a critical role in promoting immune tolerance.

Research activity

The group has contributed to the identification and the characterization of a subset of cells, named DC-10, present in vivo and inducible in vitro. DC-10 are potent tolerogenic DC characterized by the ability to secrete IL-10, and by the expression of immunomodulatory molecules including HLA-G, ILT3, and ILT4, which render them potent inducers of Ag-specific Tr1 cells. In the past years, this unit has also elucidated the mechanisms underlying the induction and functions of Tr1 cells, an inducible subset of CD4+ T regulatory cells that suppress T cell responses via IL-10.

In collaboration with the group led by Prof. Roncarolo, this unit contributed to the definition of protocols for the induction of Tr1 cells for cell-based approaches and to the discovery of specific biomarkers of Tr1 cells. In collaboration with Dr. Bacchetta, this unit also contributed to the characterization of CD25+FOXP3+ Treg cells in healthy and pathological settings and to the development of a protocol to generate them based on gene transfer of FOXP3. Finally, Dr. Annoni has developed and characterized in Maria Grazia Roncarolo’s group a lentiviral vector-based platform able to induce antigen-specific tolerance in vivo.