Vitamin D3-Induced Tolerogenic Dendritic Cells Modulate the Transcriptomic Profile of T CD4 + Cells Towards a Functional Hyporesponsiveness
The use of autologous tolerogenic dendritic cells (tolDC) has become a promising alternative for the treatment of autoimmune diseases. Among the different strategies available, the use of vitamin D3 for the generation of tolDC (vitD3-tolDC) constitutes one of the most robust approaches due to their...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:252364 |
| Acceso en línea: | https://ddd.uab.cat/record/252364 https://dx.doi.org/urn:doi:10.3389/fimmu.2020.599623 |
| Access Level: | acceso abierto |
| Palabra clave: | Tolerogenic dendritic cells Immune tolerance T cells Antigen-specific response Transcriptomic study |
| Sumario: | The use of autologous tolerogenic dendritic cells (tolDC) has become a promising alternative for the treatment of autoimmune diseases. Among the different strategies available, the use of vitamin D3 for the generation of tolDC (vitD3-tolDC) constitutes one of the most robust approaches due to their immune regulatory properties, which are currently being tested in clinical trials. However, the mechanisms that vitD3-tolDC trigger for the induction of tolerance remain elusive. For this reason, we performed a full phenotypical, functional, and transcriptomic characterization of T cells upon their interaction with autologous, antigen-specific vitD3-tolDC. We observed a strong antigen-specific reduction of T cell proliferation, combined with a decrease in the relative prevalence of T1 subpopulations and IFN- γ production. The analysis of the transcriptomic profile of T CD4 + cells evidenced a significant down-modulation of genes involved in cell cycle and cell response to mainly pro-inflammatory immune-related stimuli, highlighting the role of JUNB gene as a potential biomarker of these processes. Consequently, our results show the induction of a strong antigen-specific hyporesponsiveness combined with a reduction on the T1 immune profile of T cells upon their interaction with vitD3-tolDC, which manifests the regulatory properties of these cells and, therefore, their therapeutic potential in the clinic. https://doi.org/10.13039/5011000033295https://doi.org/10.13039/5011000033293https://doi.org/10.13039/5011000033296https://doi.org/10.13039/501100003329 https://doi.org/10.13039/501100003329_https://doi.org/10.13039/501100003329_https://doi.org/10.13039/501100003329 https://doi.org/10.13039/501100003329 |
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