Comparison of two different protocols for the induction of maturation of human dendritic cells in vitro

Čolić, Miodrag; Mojsilovic, Slavko; Pavlović, Bojan; Vučićević, Dragana; Majstorović, Ivana; Bufan, Biljana; Stojić-Vukanić, Zorica; Vasilijić, Saša; Vučević, Dragana; Gašić, Sonja; Balint, Bela

doi:10.2298/vsp0405471c

Cited by 13 publications

(7 citation statements)

References 28 publications

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“…Next, we found that iDCs differentiated with PL‐MSCs have unimpaired maturation, which is in contrast to the findings that the MSC‐mediated inhibition of DCs differentiation could not be restored with LPS, CD40L, or TNF‐α . Since phenotype, allostimulatory activity, and the abilities to overcome MSC‐mediated inhibition depend on maturation stimuli , our new finding could be a result of different agents used for the maturation. In line with this, we showed that the phenotype, although not the allostimulatory capacity, of PL‐MSC‐developed DCs could be restored by the pro‐inflammatory cocktail, but not with LPS.…”

Section: Discussioncontrasting

confidence: 58%

“…Since phenotype, allostimulatory activity, and the abilities to overcome MSCmediated inhibition depend on maturation stimuli [21,34], our new finding could be a result of different agents used for the maturation. In line with this, we showed that the phenotype, although not the allostimulatory capacity, of PL-MSC-developed DCs could be restored by the pro-inflammatory cocktail, but not with LPS.…”

Section: Discussionmentioning

confidence: 93%

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Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte‐derived dendritic cells

et al. 2013

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Immunoregulatory mechanisms within periapical lesions (PLs) are as of yet unexplored. Considering the crucial role of DCs in controlling the immune response within PLs, the immunomodulatory properties of mesenchymal stem cells (MSCs), and the colocalization of MSCs and DCs in situ, we wondered whether MSCs from PLs modulate the development and functions of DCs. Using a model of monocyte-derived DCs, we showed that PL-MSCs inhibited differentiation of DCs via soluble factors, of which IL-6 had a minor effect, but did not impair their subsequent maturation induced by pro-inflammatory cytokines. However, upon maturation such DCs favored the production of Th2/Th17 cytokines by allogenic CD4 + lymphocytes in coculture, compared with mature DCs differentiated without PL-MSCs. PL-MSC-differentiated DCs, cultivated with pro-inflammatory cytokines and PL-MSCs, although phenotypically mature, exhibited poor allostimulatory activity, induced anergy, Th2 polarization, differentiation of suppressive CD4 + CD25 high CD39 + Treg-cell subsets via IDO-1-, ILT-3-, and ILT-4-dependent mechanisms, and increased production of TGF-β in the coculture. In contrast, DCs cultivated with PL-MSCs only during maturation stimulated proliferation and Th1 polarization of CD4 + T cells in an IL-12-independent manner. In conclusion, PL-MSCs significantly modulate the development and functions of DCs, depending on the phase of DCs development during which the interaction occurs. Keywords: Dendritic cells r Mesenchymal stem cells r Periapical lesions r Th polarizationAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionPeriapical lesions (PLs) are a common pathology within the human population initiated by the bacterial invasion of the root canal and develop from an acute inflammatory response to the formation of granulomas or cysts infiltrated by various inflammatory cells [1].Correspondence: Prof. MiodragČolić e-mail: fakultet.vma@mod.gov.rs Furthermore, cytokines produced by Th cells have been shown to play a crucial role in PLs pathogenesis. Namely, Th1-and Th17-derived cytokines promote inflammation, bone resorption, and disease progression. Th2 cells seem to be important for the later phases of PLs development, whereas IL-10 and TGF-β produced by Treg cells seem to be important for the healing processes within PLs [2,3]. However, it is not yet clear which mediators and cells are involved crucially in the regulation of Th-cell commitment during the development, maintenance, and resolution of the disease.C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2013. 43: 1862-1872 Immunomodulation 1863DCs are the key regulatory and decision-making cells with a unique ability to activate naive T cells and polarize their development. These cells can be differentiated in vitro from monocytes or CD34 + -progenitors with GM-CSF and IL-4, generating CD1a + CD14 − immature DCs (iDCs) [4]. Alternatively, in the absence of IL-4, GM-CSF induces the differ...

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Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 93%

Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte‐derived dendritic cells

et al. 2013

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“…The functions of these genes are associated with inflammatory response and apoptosis. In vitro assays have clearly shown that DCs matured with this cocktail strongly stimulate the proliferation of allogeneic lymphocytes[70, 71]. …”

Section: Maturation Cocktailsmentioning

confidence: 99%

Monocyte-derived DC maturation strategies and related pathways: a transcriptional view

Castiello

Sabatino

Jin

et al. 2011

Cancer Immunol Immunother

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Ex vivo production of highly-stimulator mature Dendritic Cells (DCs) for cellular therapy has been used to treat different pathological conditions with the aim of inducing a specific immune response. In the last decade several protocols have been developed to mature monocyte-derived DCs: each one has led to the generation of DCs showing different phenotypes and stimulatory abilities, but it is not yet known which one is the best for inducing effective immune responses. We grouped several different maturation protocols according to the downstream pathways they activated and reviewed the shared features at a transcriptomic level to reveal the potential of DCs matured by each protocol to develop Th polarized immune responses.

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“…starting on day 6 or 7 of culture) with maturation or modulation agents such as TNF-alpha, PGE 2 , CpG oligonucleotides [120][121][122]. We therefore asked whether adding LY-294002 with or without ODN 1826 in post-generated DC cultures (i.e.…”

Section: Pi3k Inhibition In Post-generation DC Increases the Immunostmentioning

confidence: 99%

Phosphatidylinositol-3-kinase activity during in vitro dendritic cell generation determines suppressive or stimulatory capacity

D’Anneo

Phillips

et al. 2011

Immunol Res

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Modulating PI3K at different stages of dendritic cells (DC) generation could be a novel means to balance the generation of immunosuppressive versus immunostimulatory DC. We show that PI3K inhibition during mouse DC generation in vitro results in cells that are potently immunosuppressive and characteristic of CD8alpha- CD11c+ CD11b+ DC. These DC exhibited low surface class I and class II MHC, CD40, and CD86 and did not produce TNF-alpha. In allogeneic MLR, these DC were suppressive. Although in these mixed cultures, there was no increase in the frequency of CD4+ CD25+ Foxp3+ cells, the Foxp3 content on a per cell basis was significantly increased. Sustained TLR9 signaling in the presence of PI3K inhibition during DC generation overrode the cells' suppressive phenotype.

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Comparison of two different protocols for the induction of maturation of human dendritic cells in vitro

Abstract: The protocol based on the combination of proinflammatory cytokines and PGE2 is better for the induction of maturation of human MDDC in vitro than the protocol using LPS alone.

Cited by 13 publications

References 28 publications

Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte‐derived dendritic cells

Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte‐derived dendritic cells

Monocyte-derived DC maturation strategies and related pathways: a transcriptional view

Phosphatidylinositol-3-kinase activity during in vitro dendritic cell generation determines suppressive or stimulatory capacity

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