San Raffaele Telethon Institute for Gene Therapy

Mechanisms of peripheral tolerance

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Group Leader

Silvia Gregori

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Main interest of the Unit is to unravel the key molecular and cellular mechanisms controlling immune tolerance. The Unit aims at studying and modulating antigen(Ag)-specific immune responses, to develop efficient therapeutic approaches to (re)establish antigen-specific immune tolerance or to boost immunity in T-cell mediated diseases.

Research activity

The group focused his research on IL-10-secreting regulatory cells and contributed to the identification of DC-10 that ara present in vivo and inducible in vitro. DC-10 are tolerogenic DC that secrete IL-10 and express HLA-G and ILT4, which render them inducers of Tr1 cells. We are currently involved in defining the role of DC-10 in control immune responses healthy and pathological conditions.

Moreover, the group developed an innovative approach, based on Lentiviral Vector (LV)- mediated gene transfer to generate stable and effective human DC suitable for cell-based approaches in immune-mediated diseases. We are currently testing engineered DC in pre-clinical models in vivo and on human samples in vitro. Immune cell identity, cell fate, and functional stability are not only controlled by the expression of transcription factors, but rather determined and maintained by epigenetic modifications. Thus far, chromatin remodeling and expression of specific non-coding RNA have been studied in human T cells, including Tregs, but only limited data are available for human DC, and especially tolerogenic DC. Given the key role of epigenetics in controlling cell identity/plasticity, the group is also investigating the epigenetic landscape of tolerogenic DC and Tregs.

Finally, a number of projects aimed at understanding/modulating immune responses to specific transgenes are active in the lab. Among those, we are actively collaborating on projects aimed at defining the impact of pre-existing immune responses on ex vivo and in vivo gene therapy.