Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis
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PROVIDER: PRJNA412634 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptome analysis of different populations of human monocyte-derived myeloid cells: Autologous Tolerogenic Dendritic Cells (ATDCs), Monocyte-derived Dendritic Cells (MoDCs) and Monocyte-derived Macrophages (MoMacro)
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Project description:Transcriptional profiling of human dendritic cells (DC) comparing control (DC generated with GM-CSF plus IL-4) with three different treatments of tolerogenic (DC generated with GM-CSF plus IL-4 and IL-10, or IL-4, IL-10, and IL-6, or IL-4, IL-10, and TGF-b1) Three two-condition experiments, control (N) vs tolerogenic DC with three different treatments. Pool of 4 indivuduals for each condition. One replicate per array.
2009-11-12 | E-GEOD-18921 | biostudies-arrayexpress
Project description:Tolerogenic dendritic cells protect against acute kidney injury
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Project description:Transcriptional profiling of human dendritic cells (DC) comparing control (DC generated with GM-CSF plus IL-4) with three different treatments of tolerogenic (DC generated with GM-CSF plus IL-4 and IL-10, or IL-4, IL-10, and IL-6, or IL-4, IL-10, and TGF-b1)
2009-11-13 | GSE18921 | GEO
Project description:Dendritic cell (DC) activation and function are underpinned by profound changes in cellular metabolism. Several studies indicate that the ability of DCs to promote tolerance is dependent on catabolic metabolism. Yet the contribution of AMP-activated kinase (AMPK), a central energy sensor promoting catabolism, to DC tolerogenicity remains unknown. Here, we show that AMPK activation renders human monocyte-derived DCs tolerogenic as evidenced by an enhanced ability to drive differentiation of regulatory T cells, a process dependent on increased RALDH activity. This is accompanied by a several metabolic changes, including increased breakdown of glycerophospholipids, enhanced mitochondrial fission-dependent fatty acid oxidation, and upregulated glucose catabolism. This metabolic rewiring is functionally important as we found interference with these metabolic processes to reduce to various degrees AMPK-induced RALDH activity as well as the tolerogenic capacity of moDCs. Altogether, our findings reveal a key role for AMPK signaling in shaping DC tolerogenicity, and suggest AMPK as target to direct DC-driven tolerogenic responses in therapeutic settings.
2024-07-16 | PXD053979 | Pride
Project description:The comparative analysis of the transcriptome of tolerogenic dendritic cells (tolDC) differentiated using different stimulus (either vitamin D3, dexamethasone or rapamycin) would allow to evidence potential common genes and pathways that could explain their potency as tolerance-inducing cells.
2018-07-31 | E-MTAB-6937 | biostudies-arrayexpress
Project description:We use tolDCs from syngeneic (C57BL6) and allogeneic (BALB/c) mice to show potent renoprotective abilities in a ischemia reperfusion AKI model. Dendritic cells were derived from mice bone marrow and cultured for 7 days with GM-CSF and IL-4. Tolerogenic DCs were cultured in the same DC media but with the addition of VitD3 and IL10. LPS was added on day 6 and cells harvested for use or analysis on day 7.
2023-07-01 | GSE205322 | GEO
Project description:Human monocyte-derived dendritic cells (moDCs) have been used as an in vitro model for studying tolerance and immunity. However, the underlying metabolic states of tolerogenic (dexamethasone and vitamin D3-treated), immature and immunogenic (mature, LPS-treated) moDCs have not been completely characterized. Through transcriptomic analyses, we determined that tolerogenic moDCs exhibit augmented catabolic pathways with respect to oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO) and glycolysis. Functionally, tolerogenic moDCs showed the highest mitochondrial membrane potential, production of reactive oxygen species and superoxide, and increased mitochondrial spare respiratory capacity. Tolerogenic and mature moDCs manifested differential FAO gene expression with FAO activity being significantly higher in tolerogenic and immature moDCs than in mature. In addition, tolerogenic and mature moDCs demonstrated similar levels of glycolytic rate, but not glycolytic capacity and reserve, which were more pronounced in tolerogenic and immature moDCs. Finally, tolerogenic and immature moDCs, but not mature moDCs, showed high plasticity to compensate the intracellular ATP content after inhibition of different energetic metabolic pathways. Overall, tolerogenic moDCs exhibit a metabolic signature of increased, stable OXPHOS programing and high plasticity for metabolic adaptation. These findings provide a framework for future research of metabolic properties of human DCs.
2015-05-08 | GSE52894 | GEO
Project description:Human monocyte-derived dendritic cells (moDCs) have been used as an in vitro model for studying tolerance and immunity. However, the underlying metabolic states of tolerogenic (dexamethasone and vitamin D3-treated), immature and immunogenic (mature, LPS-treated) moDCs have not been completely characterized. Through transcriptomic analyses, we determined that tolerogenic moDCs exhibit augmented catabolic pathways with respect to oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO) and glycolysis. Functionally, tolerogenic moDCs showed the highest mitochondrial membrane potential, production of reactive oxygen species and superoxide, and increased mitochondrial spare respiratory capacity. Tolerogenic and mature moDCs manifested differential FAO gene expression with FAO activity being significantly higher in tolerogenic and immature moDCs than in mature. In addition, tolerogenic and mature moDCs demonstrated similar levels of glycolytic rate, but not glycolytic capacity and reserve, which were more pronounced in tolerogenic and immature moDCs. Finally, tolerogenic and immature moDCs, but not mature moDCs, showed high plasticity to compensate the intracellular ATP content after inhibition of different energetic metabolic pathways. Overall, tolerogenic moDCs exhibit a metabolic signature of increased, stable OXPHOS programing and high plasticity for metabolic adaptation. These findings provide a framework for future research of metabolic properties of human DCs. Total RNA of sixteen samples from four moDC types (tolerogenic, LPS-tolerogenic, immature and mature) were extracted by Trizol (Invitrogen) followed by a clean-up procedure using RNeasy Micro Kit (Qiagen). All RNA samples had an integrity number ≥9.6 assessed by Agilent Bioanalyzer. Total RNA samples were amplified using TargetAmp™ and the biotinilated cRNA was prepared by Nano-g™ Biotin-aRNA Labeling Kit for the Illumina® System (Epicentre). After the hybridization to the Illumina Human HT-12 v4 Beadchips for 17 h at 58°C, the arrays were washed, stained (Illumina Wash Protocol) and then scanned using BeadArray Scanner 500GX. Array data were extracted at the probe level without background correction using Illumina GenomeStudio software. These raw data were quantile normalized and log2 transformed. Technical replicates were obtained from the hybridization in duplicate of three samples. Pearson correlation analysis showed high correlation between the technical replicates (r>0.99). Differentially expressed genes (DEGs) were identified using Limma16 with Benjamini-Hochberg multiple testing correction (p<0.05). DEGs were further clustered into different groups according to the patterns of expression change among the different moDC types using STEM software17. The analysis was performed in R v.2.12.2 (http://www.R-project.org) with Bioconductor 2.12 (http://www.bioconductor.org) and enabled by Pipeline Pilot (www.accelrys.com).
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Project description:Understanding the molecular mechanisms that initiate and control immunosuppression by myeloid cells is essential to overcoming the myeloid-induced disbalance of the immune system observed in patients. Myeloid cells are implicated in aggravated suppression of immunity as seen in cancer as well as in defective modulation of immune responses as observed in autoimmunity. Therefore, signaling pathways controlling immunomodulation by myeloid cells are an attractive target to potentially restore immune homeostasis and increase clinical benefit for a large number of patients. Here, we used label-free quantitative proteomics to identify proteins that are differentially expressed between different myeloid cells (myeloid-derived suppressor cells (MDSCs), tolerogenic dendritic cells (TolDCs), monocyte-derived dendritic cells (MoDCs) and precursor monocytes.
2023-09-20 | PXD027715 | Pride