scholarly journals EFFECTS OF ORAL ALFACALCIDOL ON MATURATION OF DENDRITIC CELLS IN GRAVES’ DISEASE PATIENTS: A DOUBLE-BLINDED RANDOMIZED CLINICAL TRIAL

2017 ◽  
Vol 10 (6) ◽  
pp. 100 ◽  
Author(s):  
Dyah Purnamasari ◽  
Samsuridjal Djauzi ◽  
Siti Setiati ◽  
Alida Harahap ◽  
Tjokorda Gde Pemayun ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Placebo Group ◽  
Treatment Group ◽  
Interleukin 12 ◽  
Graves Disease ◽  
Hla Dr ◽  
Before And After ◽  
Double Blinded ◽  
Dc Maturation

Maturity level of dendritic cells (DC) plays a pivotal role in initiating and regulating autoimmunity. In graves’ disease (GD), DCs have more active immune responses than those in healthy subjects. Our previous study demonstrated immunoregulatory effects of in vitro 1,25-D3 on maturation of DC in GD patients. This study aims to evaluate the effect of oral 1α-D3 on DC maturation in GD patients. Methods: Twenty five GD patients with thyrotoxicosis were divided into two groups: 12 GD patients receiving oral 1α-D3 and 13 GD patients receiving placebo, in addition to treatment of propylthiouracil. Comparison of DC maturation were performed before and after the oral 1α-D3. DC maturation was assessed based on the expression of DC markers (HLA-DR, CD80, CD40, CD83, CD14 and CD206) and the ratio of cytokines interleukin-12/IL-10.Results: After 8 weeks, 8 out of 12 GD patients in treatment group and 6 out of 13 GD patients in placebo group still had high fT4 level. The expression of CD80 decreased (p=0.48) and CD206 increased (p=0.47) insignificantly among treatment group. The IL-12/IL-10 ratio decreased along with the improvement of fT4 level in both groups. No difference of the IL-12/IL10 ratio between treatment and placebo group. Conclusion: The effects of oral 1α-D3 on DC maturation of GD patients have not been clearly demonstrated in this study yet.  

scholarly journals EFFECTS OF IN VITRO 1,25 DIHYDROXYVITAMIN D ON MATURATION OF DENDRITIC CELLS IN GRAVES’ DISEASE PATIENTS

2016 ◽  
Vol 9 (5) ◽  
pp. 221
Author(s):  
Dyah Purnamasari ◽  
Samsuridjal Djauzi ◽  
Siti Setiati ◽  
Alida Harahap ◽  
Tjokorda Gde Dalem Pemayun ◽  
...  
Keyword(s):  
Vitamin D ◽  
Dendritic Cells ◽  
Lupus Erythematosus ◽  
Healthy Subjects ◽  
Human Leukocyte ◽  
Graves Disease ◽  
Autoimmune Reaction ◽  
Hla Dr ◽  
Dc Maturation

ABSTRACTObjective: The autoimmune reaction in Graves’ disease (GD) is induced by self-antigen, which is presented by dendritic cells (DCs). DCs in GD have more active immune responses than those in healthy subjects. The ability of DC as antigen-presenting cell is determined by its maturity level. InGD, vitamin D level is inversely proportional to antibody titer and proportionally associated with remission status. Studies on healthy subjects andautoimmune patients (systemic lupus erythematosus (SLE), multiple sclerosis (MS), and Crohn’s disease) have demonstrated immunoregulatoryeffects of vitamin D, mainly through inhibition of DC maturation, which may decrease the DC’s immunogenic profile. This study aims to identify theeffect of 1,25-D3 in vitro on DC maturation in patients with GD.Methods: This is an experimental study, which was conducted in 12 GD patients with thyrotoxicosis. Monocyte-derived DC of GD patients wascultured, with or without 1,25-D3 in vitro at monocytic phase. The DC maturation was then stimulated by lipopolysaccharide (LPS) and evaluatedbased on the expression of DC markers (human leukocyte antigen-D-related [HLA-DR], CD80, CD40, CD83, CD14, and CD206) and the ratio of cytokineinterleukin-12 (IL-12)/IL-10 levels in the supernatants.Results: Following the LPS stimulation, DC with 1,25-D3 showed lower expressions of HLA-DR, CD80, CD40, and CD83, and higher expressions ofCD14 and CD206 compared to DC without 1,25-D3. DC with 1,25-D3 had lower ratio of IL-12/IL-10 levels than those without 1,25-D3.Conclusion: In vitro 1,25-D3 supplementation inhibits DC maturation in patients with GD.Keywords: Vitamin D, Graves’ disease, Dendritic cells.

scholarly journals Expression of vFLIP in a Lentiviral Vaccine Vector Activates NF-κB, Matures Dendritic Cells, and Increases CD8+ T-Cell Responses

2008 ◽  
Vol 83 (4) ◽  
pp. 1555-1562 ◽  
Author(s):  
Helen M. Rowe ◽  
Luciene Lopes ◽  
Najmeeyah Brown ◽  
Sofia Efklidou ◽  
Timothy Smallie ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Tumor Therapy ◽  
T Cell Response ◽  
Vaccine Vector ◽  
Interleukin 12 ◽  
Mouse Bone Marrow ◽  
Dc Maturation

ABSTRACT Lentiviral vectors deliver antigens to dendritic cells (DCs) in vivo, but they do not trigger DC maturation. We therefore expressed a viral protein that constitutively activates NF-κB, vFLIP from Kaposi's sarcoma-associated herpesvirus (KSHV), in a lentivector to mature DCs. vFLIP activated NF-κB in mouse bone marrow-derived DCs in vitro and matured these DCs to a similar extent as lipopolysaccharide; costimulatory markers CD80, CD86, CD40, and ICAM-1 were upregulated and tumor necrosis factor alpha and interleukin-12 secreted. The vFLIP-expressing lentivector also matured DCs in vivo. When we coexpressed vFLIP in a lentivector with ovalbumin (Ova), we found an increased immune response to Ova; up to 10 times more Ova-specific CD8+ T cells secreting gamma interferon were detected in the spleens of vFLIP_Ova-immunized mice than in the spleens of mice immunized with GFP_Ova. Furthermore, this increased CD8+ T-cell response correlated with improved tumor-free survival in a tumor therapy model. A single immunization with vFLIP_Ova also reduced the parasite load when mice were challenged with OVA-Leishmania donovani. In conclusion, vFLIP from KSHV is a DC activator, maturing DCs in vitro and in vivo. This demonstrates that NF-κB activation is sufficient to induce many aspects of DC maturation and that expression of a constitutive NF-κB activator can improve the efficacy of a vaccine vector.

Comparison of 24-Hour Electrocardiogram Parameters in Patients with Graves Disease Before and After Anti-Thyroid Therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Gamze Akkuş ◽  
Yeliz Sökmen ◽  
Mehmet Yılmaz ◽  
Özkan Bekler ◽  
Oğuz Akkuş
Keyword(s):  
Treatment Group ◽  
Medical Treatment ◽  
Surgical Therapy ◽  
Graves Disease ◽  
Before And After ◽  
Euthyroid Status ◽  
Ectopic Beats ◽  
Group 2 ◽  
Electrocardiographic Parameters ◽  
Group 1

Background: We aimed prospectively investigate the laboratory and electrocardiographic parameters (hearth rate, QRS, QT, QTc, Tpe, Tpe/QTc, arrhythmia prevalance) in patients with graves disease before and after antithyroid therapy. Methods: 71 patients (48 female, 23 male), age between 18-50 (mean±SD: 36.48±12.20 ) with GD were included into the study. Patients treated with antithyroid therapy (thionamids and/or surgical therapy) to maintain euthyroid status. Patients were examined in terms of electrocardiographic parameters before and after the treatment. Results: Mean TSH, free thyroxin (fT4) and tri-iodothyrionine (fT3) levels of all patients were 0.005±0.21, 3.27± 1.81, 11.42±7.44, respectively. While 9 patients (group 2) underwent surgical therapy, had suspicious of malignant nodule or large goiter and unresponsiveness to medical treatment; the other patients (n=62, group 1) were treated with medical therapy. Patients with surgical therapy had more increased serum fT4 (p=0.045), anti-thyroglobulin value (p=0.018) and more severe graves orbitopathy (n=0.051) before treatment when compared to medical therapy group. Baseline Tpe duration and baseline Tpe/QTc ratio and frequency of supraventricular ectopic beats were found to be significantly higher in group 2 when compared to group 1 (p=0.00, p=0.005). Otherwise baseline mean heart rate, QRS duration, QTc values of both groups were similar. Although the patients became their euthyroid status, group 2 patients had still suffered from more sustained supraventricular ectopics beats than group 1. Conclusion: Distinct from medical treatment group, surgical treatment group with euthyroidism at least 3 months had still suffered from an arrhythmia (Tpe, Tpe/QTc, supraventricular and ventricular ectopic beats).

Value of Whole-Body Washing With Chlorhexidine for the Eradication of Methicillin-ResistantStaphylococcus aureus:A Randomized, Placebo-Controlled, Double-Blind Clinical Trial

2007 ◽  
Vol 28 (9) ◽  
pp. 1036-1043 ◽  
Author(s):  
C. Wendt ◽  
S. Schinke ◽  
M. Württemberger ◽  
K. Oberdorfer ◽  
O. Bock-Hensley ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Placebo Group ◽  
Treatment Group ◽  
Solution Treatment ◽  
University Hospital ◽  
Whole Body ◽  
Double Blind ◽  
Antiseptic Solution ◽  
Double Blind Clinical Trial ◽  
Double Blinded

Background.Whole-body washing with antiseptic solution has been widely used as part of eradication treatment for colonization with methicillin-resistantStaphylococcus aureus(MRSA), but evidence for the effectiveness of this measure is limited.Objective.To study the efficacy of whole-body washing with chlorhexidine for the control of MRSA.Design.Randomized, placebo-controlled, double-blinded clinical trial.Setting.University Hospital of Heidelberg and surrounding nursing homes.Patients.MRSA carriers who were not treated concurrently with antibiotics effective against MRSA were eligible for the study.Intervention.Five days of whole-body washing with either 4% chlorhexidine solution (treatment group) or with a placebo solution. All patients received mupirocin nasal ointment and chlorhexidine mouth rinse. The outcome was evaluated 3, 4, 5, 9, and 30 days after treatment with swab samples taken from several body sites.Results.Of 114 patients enrolled in the study (56 in the treatment group and 58 in the placebo group), 11 did not finish treatment (8 from the treatment group and 3 from the placebo group [P= .02]). At baseline, the groups did not differ with regard to age, sex, underlying condition, site of MRSA colonization, or history of MRSA eradication treatment. Eleven patients were MRSA-free 30 days after treatment (4 from the treatment group and 7 from the placebo group [P= .47]). Only groin-area colonization was significantly better eradicated by the use of chlorhexidine. The best predictor for total eradication was a low number of body sites positive for MRSA. Adverse effects were significantly more frequent in the treatment group than in the placebo group (any symptom, 71% vs 33%) but were reversible in most cases.Conclusion.Whole-body washing can reduce skin colonization, but it appears necessary to extend eradication measures to the gastrointestinal tract, wounds, and/or other colonized body sites if complete eradication is the goal.Trial Registration.ClinicalTrials.gov identifier: NCT00266448.

scholarly journals Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3312
Author(s):  
Matjaž Weiss ◽  
Marko Anderluh ◽  
Martina Gobec
Keyword(s):  
Dendritic Cells ◽  
Posttranslational Modification ◽  
Human Monocyte ◽  
T Cell Differentiation ◽  
Maturation Process ◽  
Hla Dr ◽  
Glcnac Transferase ◽  
And Function

The O-GlcNAcylation is a posttranslational modification of proteins regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase. These enzymes regulate the development, proliferation and function of cells, including the immune cells. Herein, we focused on the role of O-GlcNAcylation in human monocyte derived dendritic cells (moDCs). Our study suggests that inhibition of OGT modulates AKT and MEK/ERK pathways in moDCs. Changes were also observed in the expression levels of relevant surface markers, where reduced expression of CD80 and DC-SIGN, and increased expression of CD14, CD86 and HLA-DR occurred. We also noticed decreased IL-10 and increased IL-6 production, along with diminished endocytotic capacity of the cells, indicating that inhibition of O-GlcNAcylation hampers the transition of monocytes into immature DCs. Furthermore, the inhibition of OGT altered the maturation process of immature moDCs, since a CD14medDC-SIGNlowHLA-DRmedCD80lowCD86high profile was noticed when OGT inhibitor, OSMI-1, was present. To evaluate DCs ability to influence T cell differentiation and polarization, we co-cultured these cells. Surprisingly, the observed phenotypic changes of mature moDCs generated in the presence of OSMI-1 led to an increased proliferation of allogeneic T cells, while their polarization was not affected. Taken together, we confirm that shifting the O-GlcNAcylation status due to OGT inhibition alters the differentiation and function of moDCs in in vitro conditions.

scholarly journals Adenovirus-Mediated CCR7 and BTLA Overexpression Enhances Immune Tolerance and Migration in Immature Dendritic Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Haiming Xin ◽  
Jinhong Zhu ◽  
Hongcheng Miao ◽  
Zhenyu Gong ◽  
Xiaochen Jiang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Tolerance ◽  
Transplant Recipients ◽  
T Helper ◽  
T Helper 2 ◽  
Immature Dendritic Cells ◽  
And Migration ◽  
Mixed Lymphocyte Reactions ◽  
Dc Maturation

Our previous report revealed that immature dendritic cells (imDCs) with adenovirus-mediated CCR7 overexpression acquired an enhanced migratory ability but also exhibited the lower immune tolerance observed in more mature cells. In the present study, we aimed to investigate whether BTLA overexpression was sufficient to preserve immune tolerance in imDCs with exogenous CCR7 overexpression. Scanning electron microscopy and surface antigens analysis revealed that BTLA overexpression suppressed DC maturation, an effect further potentiated in CCR7 and BTLA cooverexpressing cells. Correspondingly, in vitro chemotaxis assays and mixed lymphocyte reactions demonstrated increased migratory potential and immune tolerance in CCR7 and BTLA coexpressing cells. Furthermore, CCR7 and BTLA cooverexpressed imDCs suppressed IFN-γ and IL-17 expression and promoted IL-4 and TGF-beta expression of lymphocyte, indicating an increase of T helper 2 (Th2) regulatory T cell (Treg). Thus, these data indicate that CCR7 and BTLA cooverexpression imparts an intermediate immune phenotype in imDCs when compared to that in CCR7- or BTLA-expressing counterparts that show a more immunocompetent or immunotolerant phenotype, respectively. All these results indicated that adenovirus-mediated CCR7 and BTLA overexpression could enhance immune tolerance and migration of imDCs. Our study provides a basis for further studies on imDCs in immune tolerance, with the goal of developing effective cellular immunotherapies for transplant recipients.

scholarly journals The Influence of Ouabain on Human Dendritic Cells Maturation

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
C. R. Nascimento ◽  
R. C. Valente ◽  
J. Echevarria-Lima ◽  
C. F. L. Fontes ◽  
L. de Araujo-Martins ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymphocyte Activation ◽  
Human Monocytes ◽  
Atpase Inhibitor ◽  
Gm Csf ◽  
Hla Dr ◽  
Distinct Category ◽  
Thymocyte Apoptosis ◽  
Human Dendritic Cells ◽  
Dc Maturation

Although known as a Na,K-ATPase inhibitor, several other cellular and systemic actions have been ascribed to the steroid Ouabain (Oua). Particularly in the immune system, our group showed that Ouabain acts on decreasing lymphocyte proliferation, synergizing with glucocorticoids in spontaneous thymocyte apoptosis, and also lessening CD14 expression and blocking CD16 upregulation on human monocytes. However, Ouabain effects on dendritic cells (DCs) were not explored so far. Considering the peculiar plasticity and the importance of DCs in immune responses, the aim of our study was to investigate DC maturation under Ouabain influence. To generate immature DCs, human monocytes were cultured with IL-4 and GM-CSF (5 days). To investigate Ouabain role on DC activation, DCs were stimulated with TNF-αfor 48 h in the presence or absence of Ouabain. TNF-induced CD83 expression and IL-12 production were abolished in DCs incubated with 100 nM Ouabain, though DC functional capacity concerning lymphocyte activation remained unaltered. Nevertheless, TNF-α-induced antigen capture downregulation, another maturation marker, occurred even in the presence of Ouabain. Besides, Ouabain increased HLA-DR and CD86 expression, whereas CD80 expression was maintained. Collectively, our results suggest that DCs respond to Ouabain maturating into a distinct category, possibly contributing to the balance between immunity and tolerance.

Dendritic Cells in the Normal Human Tympanic Membrane

1995 ◽  
Vol 104 (10) ◽  
pp. 803-807 ◽  
Author(s):  
Burkhard Hussl ◽  
Gisela Egg ◽  
Weija Kong ◽  
Nikolaus Romani ◽  
Annelies Schrott-Fischer
Keyword(s):  
Dendritic Cells ◽  
Tympanic Membrane ◽  
Ultrastructural Level ◽  
Dc System ◽  
Birbeck Granules ◽  
Hla Dr ◽  
Positive Immunostaining ◽  
Tympanic Membranes

Dendritic cells (DCs) are antigen-presenting cells that possess an outstanding capacity to initiate primary immune responses. They reside in the tissues in an immunologically immature state. Upon antigenic challenge in vivo or short-term culture in vitro, they undergo a maturation process and turn into mature “lymphoid DCs.” Langerhans cells (LCs) of the epidermis were identified as members of this DC system. They have been demonstrated in cholesteatoma matrix and in inflamed tympanic membranes, but the normal tympanic membrane was hitherto thought to be devoid of them. To clarify this question, we removed 12 normal tympanic membranes postmortem and processed them for a sheet preparation. The epidermal layers were peeled off and immunostained with the following monoclonal antibodies: HLA-DR, OKT6/CD1 a, and LAG (specific for the Birbeck granules of LCs). Two tympanic membranes were also processed for routine electron microscopy. In all epidermal sheets a dense network of DCs could be demonstrated. They showed a positive immunostaining reaction with HLA-DR, but a negative one with OKT6 and LAG. Thus, they differ in their immunohistochemical properties from typical epidermal LCs. At the ultrastructural level, DCs could also be identified, but without the typical Birbeck granules. This explains the negative reaction with the LAG antibody. These findings were extended and supported by a tissue culture examination of three normal tympanic membranes. After 3 days, typical “veiled” cells (ie, mature DCs), showing positive immunostaining with HLA-DR, could be recovered from the culture medium. In an oxidative mitogenesis assay, these cells displayed strong stimulatory capacity for resting T lymphocytes. The presence of DCs in the normal tympanic membrane is an important clue for a better understanding of the immune status of the middle ear.

scholarly journals Murine gammaherpesvirus-68 productively infects immature dendritic cells and blocks maturation

2007 ◽  
Vol 88 (7) ◽  
pp. 1896-1905 ◽  
Author(s):  
Romana Hochreiter ◽  
Catherine Ptaschinski ◽  
Steven L. Kunkel ◽  
Rosemary Rochford
Keyword(s):  
Dendritic Cells ◽  
Mhc Class I ◽  
Viral Reactivation ◽  
Class I ◽  
Interleukin 12 ◽  
Murine Gammaherpesvirus ◽  
Immature Dendritic Cells ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68 ◽  
Dc Maturation

Many viruses have evolved mechanisms to evade host immunity by subverting the function of dendritic cells (DCs). This study determined whether murine gammaherpesvirus-68 (γHV-68) could infect immature or mature bone-marrow-derived DCs and what effect infection had on DC maturation. It was found that γHV-68 productively infected immature DCs, as evidenced by increased viral titres over time. If DCs were induced to mature by exposure to LPS and then infected with γHV-68, only a small percentage of cells was productively infected. However, limiting-dilution assays to measure viral reactivation demonstrated that the mature DCs were latently infected with γHV-68. Electron microscopy revealed the presence of capsids in the nucleus of immature DCs but not in mature DCs. Interestingly, infection of immature DCs by γHV-68 did not result in upregulation of the co-stimulatory molecules CD80 and CD86 or MHC class I and II, or induce cell migration, suggesting that the virus infection did not induce DC maturation. Furthermore, γHV-68 infection of immature DCs did not result in elevated interleukin-12, an important cytokine in the induction of T-cell responses. Finally, lipopolysaccharide and poly(I : C) stimulation of γHV-68-infected immature DCs did not induce increases in the expression of co-stimulatory molecules and MHC class I or II compared with mock-treated cells, suggesting that γHV-68 infection blocked maturation. Taken together, these data demonstrate that γHV-68 infection of DCs differs depending on the maturation state of the DC. Moreover, the block in DC maturation suggests a possible immunoevasion strategy by γHV-68.

scholarly journals Glyceraldehyde-3-phosphate dehydrogenase from Eimeria acervulina modulates the functions of chicken dendritic cells to boost Th1 type immune response and stimulates autologous CD4+ T cells differentiation in-vitro

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Shakeel Ahmed Lakho ◽  
Muhammad Haseeb ◽  
Jianmei Huang ◽  
Zhang Yang ◽  
Muhammad Waqqas Hasan ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immunoblot Analysis ◽  
Eimeria Acervulina ◽  
Ifn Γ ◽  
Negative Controls ◽  
Th1 Polarization ◽  
Dc Maturation

AbstractDendritic cells (DCs) play a pivotal role to amplify antigen-specific immune responses. Antigens that sensitize T cells via antigen-presentation by DCs could enhance the capacity of host immunity to fight infections. In this study, we tested the immunogenic profiles of chicken DCs towards Glyceraldehyde-3-phosphate dehydrogenase from Eimeria acervulina (EaGAPDH). Immunoblot analysis showed that recombinant EaGAPDH (rEaGAPDH) protein was successfully recognized by rat sera generated against rEaGAPDH. Interaction and internalisation of rEaGAPDH by chicken splenic-derived DCs (chSPDCs) was confirmed by immunofluorescence analysis. Flow cytometry revealed that chSPDCs upregulated MHCII, CD1.1, CD11c, CD80, and CD86 cell-surface markers. Moreover, mRNA expressions of DC maturation biomarkers (CCL5, CCR7, and CD83) and TLR signalling genes (TLR15 and MyD88) were also upregulated whereas those of Wnt signalling were non-significant compared to negative controls. rEaGAPDH treatment induced IL-12 and IFN-γ secretion in chSPDCs but had no effect on IL-10 and TGF-β. Likewise, DC-T cell co-culture promoted IFN-γ secretion and the level of IL-4 was unaffected. Proliferation of T cells and their differentiation into CD3+/CD4+ T cells were triggered in chSPDCs-T cells co-culture system. Taken together, rEaGAPDH could promote Th1 polarization by activating both host DCs and T cells and sheds new light on the role of this important molecule which might contribute to the development of new DCs-based immunotherapeutic strategies against coccidiosis.

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