Journal
FRONTIERS IN IMMUNOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.01251
Keywords
tolerogenic dendritic cells; multiple sclerosis; biomarkers; vitamin D3; immune tolerance
Categories
Funding
- Plan Nacional de I+D+I [PI14/01175, PI16/01737, PI17/01521]
- Fondo Europeo de Desarrollo Regional (FEDER)
- IWT-TBM (Belgium) [140191]
- AGAUR (Agencia de Gestio d'Ajuts Universitaris i de Recerca) - Government of Catalonia
- Government of Catalonia [2017 SGR 103]
- IWT-TBM [140191]
- EU
- ISCIII-Subdireccion General de Evaluacion
- FACTT network [BM1305]
- [779316 -ReSToRe]
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The administration of autologous tolerogenic dendritic cells (tolDC) has become a promising alternative for the treatment of autoimmune diseases, such as multiple sclerosis (MS). Specifically, the use of vitamin D3 for the generation of tolDC (vitD3-tolDC) constitutes one of the most widely studied approaches, as it has evidenced significant immune regulatory properties, both in vitro and in vivo. In this article, we generated human vitD3-tolDC from monocytes from healthy donors and MS patients, characterized in both cases by a semi-mature phenotype, secretion of IL-10 and inhibition of allogeneic lymphocyte proliferation. Additionally, we studied their transcriptomic profile and selected a number of differentially expressed genes compared to control mature and immature dendritic cells for their analysis. Among them, qPCR results validated CYP24A1, MAP7 and MUCL1 genes as biomarkers of vitD3-tolDC in both healthy donors and MS patients. Furthermore, we constructed a network of protein interactions based on the literature, which manifested that MAP7 and MUCL1 genes are both closely connected between them and involved in immune-related functions. In conclusion, this study evidences that MAP7 and MUCL1 constitute robust and potentially functional biomarkers of the generation of vitD3-tolDC, opening the window for their use as quality controls in clinical trials for MS.
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