Tolerogenic dendritic cells are efficiently generated using minocycline and dexamethasone

Lee, Jaehee; Park, Chan-Su; Lim, Heeji; Kim, Ji Wan; Kim, Sang-Hyeon; Song, Sukgil; Kim, Kyungjae; Lee, Chong-Kil

doi:10.1038/s41598-017-15569-1

Cited by 39 publications

(43 citation statements)

References 48 publications

(46 reference statements)

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“… 33 Although we observed no difference in IL-10 production within 24 hours after LPS activation, the difference between mature cells and TolDCs was clear after 48 hours, indicating the tolerogenic potential of these cells. Lee et al 34 compared the effect of different stimuli (rapamycin, vitamin D3, IL-10, dexamethasone and minocycline) on DC generation with regulatory properties and observed that the level of IL-10 produced varies according to the stimulus. Further work shows that the culture time of these cells also influences the level of IL-10 produced.…”

Section: Discussionmentioning

confidence: 99%

Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation

Aragão-França

Rocha

Andrade

et al. 2018

Allergy Asthma Immunol Res

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PurposeThe use of tolerogenic dendritic cells (TolDCs) to control exacerbated immune responses may be a prophylactic and therapeutic option for application in autoimmune and allergic conditions. The objective of this work was to evaluate the effects of TolDC administration in a mouse model of allergic airway inflammation caused by mite extract.MethodsMouse bone marrow-derived TolDCs were induced by incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and dexamethasone, and then characterized by flow cytometry and cytokine production by enzyme-linked immunosorbent assay (ELISA). For the in vivo model of Blomia tropicalis-induced allergy, mice transplanted with antigen-pulsed TolDCs were sensitized intraperitoneally with B. tropicalis mite extract (BtE) adsorbed to aluminium hydroxide. After challenge by nasal administration of BtE, bronchoalveolar lavage fluid (BALF), lungs, spleen and serum were collected for analysis.ResultsInduction of TolDCs was efficiently achieved as shown by low expression of major histocompatibility complex (MHC) II, programmed death-ligand (PD-L) 2 and pro-inflammatory cytokine production, and up-regulation of interleukin (IL)-10, upon LPS stimulation in vitro. Transplantation of 1 or 2 doses of BtE-pulsed TolDCs reduced the number of inflammatory cells in BALF and lungs as well as mucus deposition. Moreover, compared to saline-injected controls, TolDC-treated mice showed lower serum levels of anti-BtE immunoglobulin E (IgE) antibodies as well as reduced Gata3 and IL-4 gene expression in the lungs and decreased IFN-γ levels in the supernatant of splenocyte cultures Transplantation of TolDCs increased the percentage of the regulatory T cells in the spleen and the lungs.ConclusionsPreventive treatment with TolDCs protects against dust mite-induced allergy in a mouse model, reinforcing the use of tolerogenic dendritic cells for the management of allergic conditions.

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Section: Discussionmentioning

confidence: 99%

Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation

Aragão-França

Rocha

Andrade

et al. 2018

Allergy Asthma Immunol Res

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“…The use of dexamethasone as an agent for the induction of tolerogenic profile in DCs has been previously shown in both mouse bone marrow cells and from human monocytes (32-34). Tolerogenic dendritic cells derived by the use of pharmacological agents, such as dexamethasone alone or in combination, and subsequently induced maturation with LPS has previously been shown to acquire stable semi-mature and tolerogenic phenotype (35)(36)(37)(38). Furthermore, the use of LPS to generate tolerogenic dendritic cells has proved to be important to favor the regulatory and migratory capacity of these cells (34).…”

Section: Discussionmentioning

confidence: 99%

Tolerogenic Dendritic Cells Reduce Cardiac Inflammation and Fibrosis in Chronic Chagas Disease

et al. 2020

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Chronic Chagas disease cardiomyopathy (CCC) is the most frequent and severe form of this parasitic disease. CCC is caused by a progressive inflammation in the heart, resulting in alterations that can culminate in heart failure and death. The use of dendritic cells (DCs) appears as an option for the development of treatments due to their important role in regulating immune responses. Here, we investigated whether tolerogenic cells (tDCs) could interfere with the progression of CCC in an experimental model of Chagas disease. The tDCs were generated and characterized as CD11b + CD11c + cells, low expression of MHC-II, CD86, CD80, and CD40, and increased expression of PD-L. These cells produced low levels of IL-6 and IL-12p70 and higher levels of IL-10, compared to mature DCs (mDCs). Interestingly, tDCs inhibited lymphoproliferation and markedly increased the population of FoxP3 + Treg cells in vitro, compared to mature DCs. In a mouse model of CCC, treatment with tDCs reduced heart inflammation and fibrosis. Furthermore, tDCs treatment reduced the gene expression of pro-inflammatory cytokines (Ifng and Il12) and of genes related to cardiac remodeling (Col1a2 and Lgals3), while increasing the gene expression of IL-10. Finally, administration of tDCs, increased the percentage of Treg cells in the hearts and spleens of chagasic mice. Ours results show that tolerogenic dendritic cells have therapeutic potential on CCC, inhibiting disease progression.

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“…Схожие результаты были получены J.-H. Le с соавт., которые в ýкспериментальных моделях показали, что различные толерогенные стимулы, в том числе и дексаметазон, приводят к увеличению количества CD86 − B7-H1 + среди DC, индуцированных IL-4 [20].…”

Section: Discussionunclassified

Phenotype and functions of human dendritic cells derived from CD14+ monocyte subsets opposed to CD16 expression

et al. 2019

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The aim of the study was to analyze the relationship between monocyte subpopulations and phenotype/ functions of monocyte-derived dendritic cells (DCs), as well as DC sensitivity to the tolerogenic effect of dexamethasone.Materials and methods. The study included 15 healthy donors. DCs were generated by cultivating enriched fractions of CD14+ monocytes with or without CD16+cell depletion (CD16-Mo-DCs or CD16+Mo-DCs, respectively) in the presence of interferon alpha (IFNα) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte subpopulations were obtained by immunomagnetic negative selection.Results. CD16+Mo-DCs were characterized by higher percentage of mature (CD83+CD14-) and lower number of semi-mature (CD14+CD83+) cells, but were similar to CD16-Mo-DCs by HLA-DR and CD86 expression, involved in the presentation of antigens and activation of naive T-cells. and also to co-inhibitory/ tolerogenic molecules B7-H1 and TLR-2. CD16+Mo-DCs displayed higher allostimulatory activity, which was positively correlated with CD86 expression (rS = 0.69; p = 0.027) and negatively – with TLR-2 expression (rS = -0.72; p = 0.1). Allostimulatory activity of CD16-Mo-DCs was positively correlated with the number of mature CD14-CD83+DCs and semi-mature CD14+CD83+DCs. Addition of dexamethasone (10-6 M) into CD16-Mo-DCs and CD16+Mo-DCs cultures led to the delay of DC maturation, the decrease of CD86 and the increase of TLR-2 expression, as well as the increase of cells with co-inhibitory CD86- B7-H1+ phenotype that was positively correlated with the reduction of DC allostimulatory activity. The decrease of CD86+/TLR-2+ index in CD16+Mo-DC population was due to the reduction of CD86+DCs and in CD16-Mo-DC population – to the increase of TLR-2+cells. Dexamethasone possessed higher inhibitory effect on DC maturation in the CD16+Mo-DC cultures.Conclusion. CD14+ monocytes, both contained and depleted by CD16+ cells, can differentiate into DCs when cultured with IFNα. The presence of CD16+ cells in whole blood monocyte pool is associated with generation of DCs showed a more mature phenotype and higher allostimulatory activity. Both CD16- and CD16+ monocyte-derived DCs are sensitive to suppressive effect of dexamethasone. However, dexamethasone tolerogenic effect involves different mechanisms in CD16-Mo-DCs and CD16+Mo-DCs.

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Tolerogenic dendritic cells are efficiently generated using minocycline and dexamethasone

Cited by 39 publications

References 48 publications

Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation

Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation

Tolerogenic Dendritic Cells Reduce Cardiac Inflammation and Fibrosis in Chronic Chagas Disease

Phenotype and functions of human dendritic cells derived from CD14+ monocyte subsets opposed to CD16 expression

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