Gram-negative enterobacteria induce tolerogenic maturation in dexamethasone conditioned dendritic cells.
Dendritic cells have been investigated in clinical trials, predominantly with the aim of stimulating immune responses against tumours or infectious diseases. Thus far, however, no clinical studies have taken advantage of their specific immunosuppressive potential. Tolerogenic DCs may represent a new...
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2012
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oai:doaj.org-article:ee96cdf8f79f412aaa9eb747b67fb4282021-11-18T08:03:30ZGram-negative enterobacteria induce tolerogenic maturation in dexamethasone conditioned dendritic cells.1932-620310.1371/journal.pone.0052456https://doaj.org/article/ee96cdf8f79f412aaa9eb747b67fb4282012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300676/?tool=EBIhttps://doaj.org/toc/1932-6203Dendritic cells have been investigated in clinical trials, predominantly with the aim of stimulating immune responses against tumours or infectious diseases. Thus far, however, no clinical studies have taken advantage of their specific immunosuppressive potential. Tolerogenic DCs may represent a new therapeutic strategy for human immune-based diseases, such as Crohn's disease, where the perturbations of the finely tuned balance between the immune system and the microflora result in disease. In the present report, we describe the generation of tolerogenic DCs from healthy donors and Crohn's disease patients using clinical-grade reagents in combination with dexamethasone as immunosuppressive agent and characterize their response to maturation stimuli. Interestingly, we found out that dexamethasone-conditioned DCs keep their tolerogenic properties to Gram-negative bacteria. Other findings included in this study demonstrate that the combination of dexamethasone with a specific cytokine cocktail yielded clinical-grade DCs with the following characteristics: a semi-mature phenotype, a pronounced shift towards anti-inflammatory versus inflammatory cytokine production and low T-cell stimulatory properties. Importantly, in regard to their clinical application, the tolerogenic phenotype of DCs remained stable after the elimination of dexamethasone and after a second stimulation with LPS or bacteria. All these properties make this cell product suitable to be tested in clinical trials of inflammatory conditions including Crohn's disease.Raquel CabezónElena RicartCarolina EspañaJulián PanésDaniel Benitez-RibasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e52456 (2012) |
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Medicine R Science Q Raquel Cabezón Elena Ricart Carolina España Julián Panés Daniel Benitez-Ribas Gram-negative enterobacteria induce tolerogenic maturation in dexamethasone conditioned dendritic cells. |
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Dendritic cells have been investigated in clinical trials, predominantly with the aim of stimulating immune responses against tumours or infectious diseases. Thus far, however, no clinical studies have taken advantage of their specific immunosuppressive potential. Tolerogenic DCs may represent a new therapeutic strategy for human immune-based diseases, such as Crohn's disease, where the perturbations of the finely tuned balance between the immune system and the microflora result in disease. In the present report, we describe the generation of tolerogenic DCs from healthy donors and Crohn's disease patients using clinical-grade reagents in combination with dexamethasone as immunosuppressive agent and characterize their response to maturation stimuli. Interestingly, we found out that dexamethasone-conditioned DCs keep their tolerogenic properties to Gram-negative bacteria. Other findings included in this study demonstrate that the combination of dexamethasone with a specific cytokine cocktail yielded clinical-grade DCs with the following characteristics: a semi-mature phenotype, a pronounced shift towards anti-inflammatory versus inflammatory cytokine production and low T-cell stimulatory properties. Importantly, in regard to their clinical application, the tolerogenic phenotype of DCs remained stable after the elimination of dexamethasone and after a second stimulation with LPS or bacteria. All these properties make this cell product suitable to be tested in clinical trials of inflammatory conditions including Crohn's disease. |
format |
article |
author |
Raquel Cabezón Elena Ricart Carolina España Julián Panés Daniel Benitez-Ribas |
author_facet |
Raquel Cabezón Elena Ricart Carolina España Julián Panés Daniel Benitez-Ribas |
author_sort |
Raquel Cabezón |
title |
Gram-negative enterobacteria induce tolerogenic maturation in dexamethasone conditioned dendritic cells. |
title_short |
Gram-negative enterobacteria induce tolerogenic maturation in dexamethasone conditioned dendritic cells. |
title_full |
Gram-negative enterobacteria induce tolerogenic maturation in dexamethasone conditioned dendritic cells. |
title_fullStr |
Gram-negative enterobacteria induce tolerogenic maturation in dexamethasone conditioned dendritic cells. |
title_full_unstemmed |
Gram-negative enterobacteria induce tolerogenic maturation in dexamethasone conditioned dendritic cells. |
title_sort |
gram-negative enterobacteria induce tolerogenic maturation in dexamethasone conditioned dendritic cells. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doaj.org/article/ee96cdf8f79f412aaa9eb747b67fb428 |
work_keys_str_mv |
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_version_ |
1718422639923429376 |