Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer
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 to...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01260/full |
| _version_ | 1819091854290845696 |
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| author | Michela Comi Giada Amodio Laura Passeri Marta Fortunato Francesca Romana Santoni de Sio Grazia Andolfi Anna Kajaste-Rudnitski Fabio Russo Luca Cesana Silvia Gregori |
| author_facet | Michela Comi Giada Amodio Laura Passeri Marta Fortunato Francesca Romana Santoni de Sio Grazia Andolfi Anna Kajaste-Rudnitski Fabio Russo Luca Cesana Silvia Gregori |
| author_sort | Michela Comi |
| collection | DOAJ |
| description | 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. DCIL−10 are mature DC, modulate T cell responses, promote T regulatory cells, and are phenotypically and functionally stable upon stimulation. Adoptive transfer of human DCIL−10 in a humanized mouse model dampens allogeneic T cell recall responses, while murine DCIL−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. |
| first_indexed | 2024-12-21T22:46:20Z |
| format | Article |
| id | doaj.art-a58d353b839e4927b6cd7f1f1af4d931 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T22:46:20Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a58d353b839e4927b6cd7f1f1af4d9312022-12-21T18:47:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-06-011110.3389/fimmu.2020.01260548425Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene TransferMichela ComiGiada AmodioLaura PasseriMarta FortunatoFrancesca Romana Santoni de SioGrazia AndolfiAnna Kajaste-RudnitskiFabio RussoLuca CesanaSilvia GregoriThe 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. DCIL−10 are mature DC, modulate T cell responses, promote T regulatory cells, and are phenotypically and functionally stable upon stimulation. Adoptive transfer of human DCIL−10 in a humanized mouse model dampens allogeneic T cell recall responses, while murine DCIL−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.https://www.frontiersin.org/article/10.3389/fimmu.2020.01260/fulldendritic cellsIL-10cell therapyimmune toleranceallogeneic transplantation |
| spellingShingle | Michela Comi Giada Amodio Laura Passeri Marta Fortunato Francesca Romana Santoni de Sio Grazia Andolfi Anna Kajaste-Rudnitski Fabio Russo Luca Cesana Silvia Gregori Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer Frontiers in Immunology dendritic cells IL-10 cell therapy immune tolerance allogeneic transplantation |
| title | Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer |
| title_full | Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer |
| title_fullStr | Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer |
| title_full_unstemmed | Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer |
| title_short | Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer |
| title_sort | generation of powerful human tolerogenic dendritic cells by lentiviral mediated il 10 gene transfer |
| topic | dendritic cells IL-10 cell therapy immune tolerance allogeneic transplantation |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01260/full |
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