Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer

• Published in: Frontiers in immunology Vol. 11; p. 1260
• Main Authors: Comi, Michela, Amodio, Giada, Passeri, Laura, Fortunato, Marta, Santoni de Sio, Francesca Romana, Andolfi, Grazia, Kajaste-Rudnitski, Anna, Russo, Fabio, Cesana, Luca, Gregori, Silvia
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 30.06.2020
• Subjects: allogeneic transplantation; Animals; cell therapy; dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Gene Expression; Genetic Vectors - genetics; Humans; IL-10; immune tolerance; Immune Tolerance - genetics; Immunology; Immunophenotyping; Interleukin-10 - genetics; Lentivirus - genetics; Mice; Monocytes - immunology; Monocytes - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transduction, Genetic; immune tolerance; dendritic cells; allogeneic transplantation; cell therapy; IL-10
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.01260

The prominent role of dendritic cells (DC) in promoting tolerance and the development of methods to generate clinical grade products allowed the clinical application of tolerogenic DC (tolDC)-based therapies for controlling unwanted immune responses. We established an efficient method to generate tolerogenic human DC, producing supra-physiological levels of IL-10, by genetically engineering monocyte-derived DC with a bidirectional Lentiviral Vector (bdLV) encoding for IL-10 and a marker gene. DC IL−10 are mature DC, modulate T cell responses, promote T regulatory cells, and are phenotypically and functionally stable upon stimulation. Adoptive transfer of human DC IL−10 in a humanized mouse model dampens allogeneic T cell recall responses, while murine DC IL−10 delays acute graft-vs.-host disease in mice. Our report outlines an efficient method to transduce human myeloid cells with large-size LV and shows that stable over-expression of IL-10 generates an effective cell product for future clinical applications in the contest of allogeneic transplantation.