Transfection of Vitamin D3-Induced Tolerogenic Dendritic Cells for the Silencing of Potential Tolerogenic Genes. Identification of CSF1R-CSF1 Signaling as a Glycolytic Regulator.
María José MansillaÍñigo González-LarreateguiNeus Figa-MartínJaume BarallatFederico FondelliAres Sellés-RiusBibiana Quirant-SánchezAina Teniente-SerraEva M Martínez-CáceresPublished in: International journal of molecular sciences (2021)
The use of autologous tolerogenic dendritic cells (tolDC) has become a promising strategy to re-establish immune tolerance in autoimmune diseases. Among the different strategies available, the use of vitamin D3 for the generation of tolDC (VitD3-tolDC) has been widely tested because of their immune regulatory properties. To identify molecules and pathways involved in the generation of VitD3-tolDC, we established an easy and fast gene silencing method based on the use of Viromer blue to introduce siRNA into monocytes on day 1 of culture differentiation. The analysis of the effect of CD209 (DC-SIGN) and CD115 (CSF1R) down-modulation on the phenotype and functionality of transfected VitD3-tolDC revealed a partial role of CD115 in their tolerogenicity. Further investigations showed that CSF1R-CSF1 signaling is involved in the induction of cell metabolic reprogramming, triggering glycolysis to produce high amounts of lactate, a novel suppressive mechanism of T cell proliferation, recently found in autologous tolerogenic dendritic cells (ATDCs).
Keyphrases
- dendritic cells
- regulatory t cells
- immune response
- cell proliferation
- cell therapy
- bone marrow
- single cell
- cerebrospinal fluid
- transcription factor
- nk cells
- drug delivery
- cell cycle
- platelet rich plasma
- high glucose
- risk assessment
- mesenchymal stem cells
- dna methylation
- endothelial cells
- genome wide
- climate change
- diabetic rats
- oxidative stress
- peripheral blood
- gene expression
- pi k akt
- bioinformatics analysis
- genome wide analysis