General autoimmunity

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Generation Of Powerful Human Tolerogenic Dendritic Cells By LV-mediated Human IL-10 Gene Transfer

Friday, June 16
4:45 PM - 5:00 PM

Tolerogenic dendritic cells (tolDC) are a promising tool for cell-based approaches to induce tolerance in transplantation and autoimmunity. Among others, IL-10-modulated DC have been recently identified as the best-suited cells for tolDC-based therapies. An example of tolDC are DC-10, an inducible subset of human DC endowed with the ability of spontaneously and upon activation releasing high levels of IL-10, and of inducing T regulatory Type 1 (Tr1) cells. In this study, we assessed the use of a lentiviral vector encoding for IL-10 and ∆NGFR, as marker gene (LV-IL-10/∆NGFR), to generate DC-10-like cells. During human DC differentiation, monocytes were treated with viral-like particles containing the simian immunodeficiency virus (SIV)-derived accessory protein Vpx and then transduced with LV-IL-10/∆NGFR. As control, classical DC-10 generated from monocytes in the presence of IL-10 were used. Compared to classical DC-10, IL-10-transduced DC secreted spontaneously, and upon LPS stimulation, higher levels of IL-10, in the absence of IL-12. Moreover, IL-10-transduced DC displayed DC-10 features: expression of the tolerogenic molecules HLA-G and ILT4, induction of hypo-responsiveness in allogeneic CD4+ and CD8+ T cells, and of anergic allo-specific T cells. Interestingly, IL-10-transduced DC are more powerful than classical DC-10 in promoting in vitro differentiation of allo-specific Tr1 cells. These results showed that constitutive over-expression of IL-10 in human monocyte-derived DC leads to a cell population that recapitulates phenotype and functions of DC-10 and open new perspectives in their clinical use in T-cell mediated diseases.

Michela Comi

San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy

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Grazia Andolfi

San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy

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Giada Amodio

San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy

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Luca Cesana

San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy

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Anna Kajaste-Rudnitski

San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy

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Silvia Gregori

Group Leader
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy

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Generation Of Powerful Human Tolerogenic Dendritic Cells By LV-mediated Human IL-10 Gene Transfer



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