Understanding dendritic cell biology and its role in immunological disorders through proteomic profiling

Ferreira, Gabriela B; Mathieu, Chantal; Overbergh, Lut

doi:10.1002/prca.200900162

Cited by 9 publications

(12 citation statements)

References 119 publications

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“…Over the past decade, proteomics has been utilised to determine differences between various immune cells [23] and in particular to study differences between whole cell extracts from immature DCs and differentially matured DCs with various PAMPs [24]. Mainly, these studies have employed 2-DE-based proteomics and highlighted changes in the expression of cytoskeletal and cytoplasmic molecules needed for basic cellular functions [12–14,25].…”

Section: Discussionmentioning

confidence: 99%

Plasma membrane proteomes of differentially matured dendritic cells identified by LC–MS/MS combined with iTRAQ labelling

Ferret‐Bernard

Castro-Borges²,

Dowle³

et al. 2012

Journal of Proteomics

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Dendritic cells (DCs) play a pivotal role in polarising Th lymphocyte subsets but it is unclear what molecular events occur when DCs generate Th2-type responses. Here, we analysed plasma membrane-enriched fractions from immature, pro-Th1 and pro-Th2 DCs and used a combination of iTRAQ labelling and LC–MS/MS to quantify changes in the proteomes. Analysis was performed on triplicate biological samples and changes verified by flow cytometry. MHC class II molecules and CD29 were up-regulated in pro-Th1 DCs whilst CD18 and CD44 were up-regulated in pro-Th2 DCs. One of the most down-regulated molecules in pro-Th1 DCs was YM-1 whilst the greatest decrease in pro-Th2 DCs was NAP-22. Other molecules up-regulated in pro-Th2 DC compared to pro-Th1 DCs included some potentially involved in protein folding during antigen processing (clathrin and Rab-7), whilst other non-membrane proteins such as enzymes/transporters related to cell metabolism (malate dehydrogenase, pyruvate kinase, and ATPase Na+/K+) were also recorded. This suggests that pro-Th2 DCs are more metabolically active while pro-Th1 DCs have a mature ‘end state’. Overall, although several molecules were preferentially expressed on pro-Th2 DCs, our proteomics data support the view of a ‘limited maturation’ of pro-Th2 DCs compared to pro-Th1 DCs.

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Section: Discussionmentioning

confidence: 99%

Plasma membrane proteomes of differentially matured dendritic cells identified by LC–MS/MS combined with iTRAQ labelling

Ferret‐Bernard

Castro-Borges²,

Dowle³

et al. 2012

Journal of Proteomics

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“…Gene expression data and proteomics have revealed considerable changes in metabolic pathways in tolDCs induced by VitD3 or VitD3-Dex ( 16 , 25 , 66 , 67 ), which might affect the microenvironment where tolDCs exert their tolerogenic function. Interestingly, tolDCs induced by other agents such as dexamethasone alone or rapamycin did not show similar metabolic changes ( 68 ).…”

Section: Potential Metabolic Effects Of Toldcsmentioning

confidence: 99%

Translating Mechanism of Regulatory Action of Tolerogenic Dendritic Cells to Monitoring Endpoints in Clinical Trials

2017

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Tolerogenic dendritic cells (tolDCs) have reached patients with autoimmune and inflammatory disease, at least in clinical trials. The safety of tolDCs as intervention therapy has been established, but the capacity to modulate autoimmune response in vivo remains to be demonstrated. Studies have revealed a diversity of regulatory mechanisms that tolDCs may employ in vivo. These mechanisms differ between various types of modulated tolDC. The most often foreseen action of tolDCs is through regulatory polarization of naïve T cells or activation of existing regulatory T cells, which should ultimately diminish autoimmune inflammation. Yet, selection of a target autoantigen remains critical to expedite tissue specific tolerance induction, while measuring immune modulation incited by tolDCs in vivo provides a great challenge. We will discuss the regulatory action of different types of tolDCs and the possible methods to monitor immunological efficacy endpoints for the next generation clinical trials.

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“…Such approaches do not allow for highthroughput analysis of many different conditions or biological replicates, which might explain why only a few proteins were found in common between different reports [10,11,14,15,32] . Here, we used ion traps for tandem mass spectrometry and LC-FTICRMS for label-and gel-free quantitation.…”

Section: Discussionmentioning

confidence: 99%

Human Dendritic Cells with Th2-Polarizing Capacity: Analysis Using Label-Free Quantitative Proteomics

Hussaarts

Kaisar²,

Güler³

et al. 2017

Int Arch Allergy Immunol

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Background: Dendritic cells (DCs) are the sentinels of the immune system. Upon recognition of a pathogen, they mature and migrate to draining lymph nodes to prime and polarize T cell responses. Although it is known that helminths and helminth-derived molecules condition DCs to polarize T helper (Th) cells towards Th2, the underlying mechanisms remain incompletely understood. Objectives: The aim of this study was to conduct a proteome analysis of helminth antigen-stimulated DCs in order to gain more insight into the cellular processes associated with their ability to polarize immune responses. Methods: We analyzed the maturation and polarization of monocyte-derived DCs from 9 donors at 2 different time points after stimulation with different Th1- and Th2-polarizing pathogen-derived molecules. The samples were measured using liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry for relative quantitation. Results: Lipopolysaccharide-induced maturation promoted the expression of proteins related to metabolic, cellular, and immune system processes. Th1-polarizing DCs, conditioned by IFN-γ during maturation, displayed accelerated maturation by differentially expressing cytoskeletal proteins and proteins involved in immune regulation. The stimulation of DCs with soluble egg antigens and omega-1 derived from Schistosoma mansoni, which are both Th2-inducing stimuli, increased 60S acidic ribosomal protein P2, and vesicle amine transferase 1 while decreasing the expression of proteins related to antigen processing and presentation. Conclusion: Our data indicate that not only proteins involved in the interaction between T cells and DCs at the level of the immunological synapse, but also those related to cellular metabolism and stress, may promote Th2 polarization.

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Understanding dendritic cell biology and its role in immunological disorders through proteomic profiling

Cited by 9 publications

References 119 publications

Plasma membrane proteomes of differentially matured dendritic cells identified by LC–MS/MS combined with iTRAQ labelling

Plasma membrane proteomes of differentially matured dendritic cells identified by LC–MS/MS combined with iTRAQ labelling

Translating Mechanism of Regulatory Action of Tolerogenic Dendritic Cells to Monitoring Endpoints in Clinical Trials

Human Dendritic Cells with Th2-Polarizing Capacity: Analysis Using Label-Free Quantitative Proteomics

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