Tolerogenic dendritic cells generated with dexamethasone and vitamin D3 regulate rheumatoid arthritis CD4+ T cells partly via transforming growth factor-<b>β</b>1

Anderson, Amy E.; Swan, David J.; Wong, Oi Yean; Buck, Matthew R.; Eltherington, Oliver; Harry, Rachel A.; Patterson, Angela; Pratt, Arthur G.; Reynolds, Gary; Doran, John‐Paul; Kirby, John A.; Isaacs, John D.; Hilkens, Catharien M. U.

doi:10.1111/cei.12870

Cited by 56 publications

(54 citation statements)

References 32 publications

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“…Another relation extracted was between tolerogenic dendritic cells and TGFB1. In this case, the source article establishes the importance of TGFB1 in immunotherapies using tolerogenic dendritic cells ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Generating a Tolerogenic Cell Therapy Knowledge Graph from Literature

et al. 2017

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Tolerogenic cell therapies provide an alternative to conventional immunosuppressive treatments of autoimmune disease and address, among other goals, the rejection of organ or stem cell transplants. Since various methodologies can be followed to develop tolerogenic therapies, it is important to be aware and up to date on all available studies that may be relevant to their improvement. Recently, knowledge graphs have been proposed to link various sources of information, using text mining techniques. Knowledge graphs facilitate the automatic retrieval of information about the topics represented in the graph. The objective of this work was to automatically generate a knowledge graph for tolerogenic cell therapy from biomedical literature. We developed a system, ICRel, based on machine learning to extract relations between cells and cytokines from abstracts. Our system retrieves related documents from PubMed, annotates each abstract with cell and cytokine named entities, generates the possible combinations of cell–cytokine pairs cooccurring in the same sentence, and identifies meaningful relations between cells and cytokines. The extracted relations were used to generate a knowledge graph, where each edge was supported by one or more documents. We obtained a graph containing 647 cell–cytokine relations, based on 3,264 abstracts. The modules of ICRel were evaluated with cross-validation and manual evaluation of the relations extracted. The relation extraction module obtained an F-measure of 0.789 in a reference database, while the manual evaluation obtained an accuracy of 0.615. Even though the knowledge graph is based on information that was already published in other articles about immunology, the system we present is more efficient than the laborious task of manually reading all the literature to find indirect or implicit relations. The ICRel graph will help experts identify implicit relations that may not be evident in published studies.

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Section: Discussionmentioning

confidence: 99%

Generating a Tolerogenic Cell Therapy Knowledge Graph from Literature

et al. 2017

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“…Common methods include inhibiting the expression of immune-stimulatory molecules (CD80/CD86 and IL-2)28–30 or stimulating constitutive expression of immunosuppressive molecules such as IL-4, IL-10 and CTLA-4,31–35 through genetic engineering. Also, exposing differentiating DC ex-vivo to drugs such as dexamethasone and vitamin D336 37 or immunosuppressive cytokines such as IL-10 and TGF-β38–40 and lipopolysaccharides41 can be used to produce tolDC. These and other methods have been extensively reviewed elsewhere 42…”

Section: Tolerogenic Cell Typesmentioning

confidence: 99%

Tolerising cellular therapies: what is their promise for autoimmune disease?

Mosanya

Isaacs

2018

Ann Rheum Dis

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The current management of autoimmunity involves the administration of immunosuppressive drugs coupled to symptomatic and functional interventions such as anti-inflammatory therapies and hormone replacement. Given the chronic nature of autoimmunity, however, the ideal therapeutic strategy would be to reinduce self-tolerance before significant tissue damage has accrued. Defects in, or defective regulation of, key immune cells such as regulatory T cells have been documented in several types of human autoimmunity. Consequently, it has been suggested that the administration of ex vivo generated, tolerogenic immune cell populations could provide a tractable therapeutic strategy. Several potentially tolerogenic cellular therapies have been developed in recent years; concurrent advances in cell manufacturing technologies promise scalable, affordable interventions if safety and efficacy can be demonstrated. These therapies include mesenchymal stromal cells, tolerogenic dendritic cells and regulatory T cells. Each has advantages and disadvantages, particularly in terms of the requirement for a bespoke versus an ‘off-the-shelf’ treatment but also their suitability in particular clinical scenarios. In this review, we examine the current evidence for these three types of cellular therapy, in the context of a broader discussion around potential development pathway(s) and their likely future role. A brief overview of preclinical data is followed by a comprehensive discussion of human data.

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“…Interestingly, the function of the proteins encoded by all these genes is strongly related to the modulation of the immune system. Surprisingly, however, there was a pool of genes that were only described for vtdx-tolDC but not for either dexa-tolDC nor vitD3-tolDC, such as CTSB, DHRS9 (dehydrogenase/reductase 9), FTH1 (ferritin heavy chain 1), RGCC (regulator of cell cycle), SLC11A1 (solute carrier family 11 member 1), TBET or TGFB1 ( 49 , 50 , 51 ). Indeed, after our study, it is worth noting that out of 64 up-modulated genes and/or proteins reported for dexa-tolDC, 29 genes for vitD3-tolDC and 102 genes for vtdx-tolDC, only 4 genes could be found in common between vtdx-tolDC and each treatment separately, as shown in the Venn diagram in Figure 1 .…”

Section: Tolerogenic Dendritic Cells As Key Tolerance-inducing Playermentioning

confidence: 99%

Searching for the Transcriptomic Signature of Immune Tolerance Induction—Biomarkers of Safety and Functionality for Tolerogenic Dendritic Cells and Regulatory Macrophages

2018

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The last years have witnessed a breakthrough in the development of cell-based tolerance-inducing cell therapies for the treatment of autoimmune diseases and solid-organ transplantation. Indeed, the use of tolerogenic dendritic cells (tolDC) and regulatory macrophages (Mreg) is currently being tested in Phase I and Phase II clinical trials worldwide, with the aim of finding an effective therapy able to abrogate the inflammatory processes causing these pathologies without compromising the protective immunity of the patients. However, there exists a wide variety of different protocols to generate human tolDC and Mreg and, consequently, the characteristics of each product are heterogeneous. For this reason, the identification of biomarkers able to define their functionality (tolerogenicity) is of great relevance, on the one hand, to guarantee the safety of tolDC and Mreg before administration and, on the other hand, to compare the results between different cell products and laboratories. In this article, we perform an exhaustive review of protocols generating human tolDC and Mreg in the literature, aiming to elucidate if there are any common transcriptomic signature or potential biomarkers of tolerogenicity among the different approaches. However, and although several effectors seem to be induced in common in some of the most reported protocols to generate both tolDC or Mreg, the transcriptomic profile of these cellular products strongly varies depending on the approach used to generate them.

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Tolerogenic dendritic cells generated with dexamethasone and vitamin D3 regulate rheumatoid arthritis CD4+ T cells partly via transforming growth factor-β1

Cited by 56 publications

References 32 publications

Generating a Tolerogenic Cell Therapy Knowledge Graph from Literature

Generating a Tolerogenic Cell Therapy Knowledge Graph from Literature

Tolerising cellular therapies: what is their promise for autoimmune disease?

Searching for the Transcriptomic Signature of Immune Tolerance Induction—Biomarkers of Safety and Functionality for Tolerogenic Dendritic Cells and Regulatory Macrophages

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