scholarly journals HUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-1

2021 ◽  
Vol 9 ◽  
Author(s):  
Jianqin Li ◽  
Yalin Xia ◽  
Xiaoru Fan ◽  
Xiaofang Wu ◽  
Feiyun Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Treg Cell ◽  
Immune Thrombocytopenic Purpura ◽  
Peripheral Blood ◽  
Mrna Level ◽  
Treg Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Thrombocytopenic Purpura ◽  
Immune Imbalance ◽  
And Function

Background: Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder and the decreased number and immunosuppressive dysfunction of Treg cells are key promoters of ITP. However, their mechanisms in ITP development have not been fully clarified.Methods: HUWE1 mRNA and protein levels in CD4+ T cells in peripheral blood from ITP patients were assessed by quantitative real-time PCR and Western blot. HUWE1 function in ITP was estimated using flow cytometry, enzyme-linked immunosorbent assay and immunosuppression assay. Besides, the HUWE1 mechanism in reducing the number and function of Treg cells in ITP was investigated by immunoprecipitation, cycloheximide-chase assay, ubiquitin experiment and immunofluorescence assay.Results: HUWE1 expression was elevated in CD4+ T cells in peripheral blood from ITP patients and HUWE1 mRNA level was negatively correlated with platelet counts and Treg cell percentage. Moreover, the interference with HUWE1 increased the number of Treg cells and enhanced its immunosuppressive function, and the HUWE1 overexpression produced the opposite results. For the exploration of mechanism, HUWE1 interacted with E26 transformation-specific-1 (Ets-1) and this binding was dependent on the negative regulation of the phosphorylation level of Ets-1 (Thr38) and HUWE1 facilitated the ubiquitin degradation of Ets-1 protein to restrain Treg cell differentiation and weaken their immunosuppressive functions. The in vivo assay confirmed that the HUWE1 inhibitor alleviated ITP in mice.Conclusion: HUWE1 induced the immune imbalance in ITP by decreasing the number and weakening the function of Treg cells through the ubiquitination degradation of Ets-1.

scholarly journals FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 4953-4960 ◽  
Author(s):  
Mojgan Ahmadzadeh ◽  
Aloisio Felipe-Silva ◽  
Bianca Heemskerk ◽  
Daniel J. Powell ◽  
John R. Wunderlich ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Metastatic Melanoma ◽  
Treg Cell ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Production Capacity ◽  
Biological Marker ◽  
Foxp3 Expression ◽  
Treg Cells

Abstract Regulatory T (Treg) cells are often found in human tumors; however, their functional characteristics have been difficult to evaluate due to low cell numbers and the inability to adequately distinguish between activated and Treg cell populations. Using a novel approach, we examined the intracellular cytokine production capacity of tumor-infiltrating T cells in the single-cell suspensions of enzymatically digested tumors to differentiate Treg cells from effector T cells. Similar to Treg cells in the peripheral blood of healthy individuals, tumor-infiltrating FOXP3+CD4 T cells, unlike FOXP3− T cells, were unable to produce IL-2 and IFN-γ upon ex vivo stimulation, indicating that FOXP3 expression is a valid biological marker for human Treg cells even in the tumor microenvironment. Accordingly, we enumerated FOXP3+CD4 Treg cells in intratumoral and peritumoral sections of metastatic melanoma tumors and found a significant increase in proportion of FOXP3+CD4 Treg cells in the intratumoral compared with peritumoral areas. Moreover, their frequencies were 3- to 5-fold higher in tumors than in peripheral blood from the same patients or healthy donors, respectively. These findings demonstrate that the tumor-infiltrating CD4 Treg cell population is accurately depicted by FOXP3 expression, they selectively accumulate in tumors, and their frequency in peripheral blood does not properly reflect tumor microenvironment.

scholarly journals Androgen receptor modulates Foxp3 expression in CD4+CD25+Foxp3+ regulatory T-cells

2015 ◽  
Vol 26 (15) ◽  
pp. 2845-2857 ◽  
Author(s):  
Magdalena Walecki ◽  
Florian Eisel ◽  
Jörg Klug ◽  
Nelli Baal ◽  
Agnieszka Paradowska-Dogan ◽  
...  
Keyword(s):  
T Cells ◽  
Androgen Receptor ◽  
Treg Cell ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Strong Increase ◽  
Histone H4 ◽  
And Function

CD4+CD25+Foxp3+ regulatory T (Treg) cells are able to inhibit proliferation and cytokine production in effector T-cells and play a major role in immune responses and prevention of autoimmune disease. A master regulator of Treg cell development and function is the transcription factor Foxp3. Several cytokines, such as TGF-β and IL-2, are known to regulate Foxp3 expression as well as methylation of the Foxp3 locus. We demonstrated previously that testosterone treatment induces a strong increase in the Treg cell population both in vivo and in vitro. Therefore we sought to investigate the direct effect of androgens on expression and regulation of Foxp3. We show a significant androgen-dependent increase of Foxp3 expression in human T-cells from women in the ovulatory phase of the menstrual cycle but not from men and identify a functional androgen response element within the Foxp3 locus. Binding of androgen receptor leads to changes in the acetylation status of histone H4, whereas methylation of defined CpG regions in the Foxp3 gene is unaffected. Our results provide novel evidence for a modulatory role of androgens in the differentiation of Treg cells.

T Regulatory Cell Activation Exists in Pathogenesis of Polycythaemia Vera.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4642-4642
Author(s):  
Xin Wang ◽  
Wenbo Zhao ◽  
Yanxia Liu ◽  
Ying Li
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Protein Level ◽  
Treg Cells ◽  
T Cell Immunity ◽  
Polycythaemia Vera ◽  
Cell Immunity ◽  
And Function ◽  
Hematopoietic Activity

Abstract Polycythaemia vera (PV) is a clonal disorder arising from a pluripotent hematopoietic progenitor cell. The etiology of PV remains unknown and there is no consensus as to the optimal therapy for this disorder. T regulatory (Treg) cells play a vital role in the maintenance of self-tolerance, control of auto-immunity and regulation of T-cell homeostasis, and they modulate overall immune responses against a variety of pathogens. Recent studies revealed that Treg cells play a crucial role in the process of hematopoietic activity. However, the effect of Treg cells in PV has not been reported. The Treg cells might participate in the dysfunction of T-cell immunity in PV. The profile and function of Treg cells in PV patients were explored in this study. Peripheral blood was withdrawn from 21 PV patients (Female 8 ; Male 13), as well as 25 age-matched healthy donors (F 9 ; M 16) as controls. All samples were taken after informed consent and collected from PV patients prior to treatment. Diagnoses of PV were made according to clinical and laboratory criteria. The peripheral blood mononuclear cells (PBMCs) were subjected to flow cytometry analyses after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Real-time PCR and Western blotting were also performed to identify quantitative FOXP3 mRNA expression and protein level in the PBMCs from PV in comparison to controls. The relationships between the percentage of Treg cells, the expressions for quantitative mRNA and protein, with the clinical data were assessed. The percentage of CD4+ T-cells was significant decreased in the group of PV than in normal control (28.7±7.07% vs 38.6±8.38%, p<0.05). But the percentage of CD4+CD25+FOXP3+ T-cells (Treg cells) in PV patients was significantly increased when compared to the control (10.93±4.02% vs 5.86±1.99%, p<0.05). Moreover, the quantitative mRNA expression of FOXP3 (64.23±18.52 vs 16.06±4.78, p<0.05) and protein expression of FOXP3 (0.74±0.16 vs 0.62±0.10, p<0.05)) were significantly enhanced in PV patients (shown in Figure 1). In conclusion, we showed that patients with PV have enhanced percentage of Treg cells in their peripheral blood. This was substantiated further with the finding that overexpressions of FOXP3 in PV both in mRNA and protein level. These results highlight important Treg-cell abnormalities in patients with PV because natural Treg cells are significantly increased in number and function. The underlying mechanism is still undefined, but the increased frequency and function of Treg cells might account for the abnormal T cell immunity in PV patients. It was suggested that there may be differently suppressive machanisms for Treg in these patients. The elevated Treg cells in PV might be activated and then affect the hematopoietic activity. We believe that Treg cells might involved in the dysfunction of T/NK cells in their disability to downregulate the hematopoietic proliferation in PV. And the expansion of Treg cells may be a feature of PV and associated with the pathogenesis of PV. Further investigation in this abnormality might provide novel therapy clue for this disease. Figure Figure

Human CD4+ CD25+ Regulatory T Cells Effectively Control Xenogeneic-GvHD Induced by Autologous T Cells in Rag2−/− γc−/− Immune-Deficient Mice.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 301-301
Author(s):  
Tuna Mutis ◽  
Rozemarijn S. van Rijn ◽  
Elles R. Simonetti ◽  
Tineke Aarts ◽  
Maarten Emmelot ◽  
...  
Keyword(s):  
T Cells ◽  
Treg Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Treg Cells ◽  
Effector T Cells ◽  
Graft Versus Host ◽  
Cell Engraftment ◽  
High Doses ◽  
The Impact

Abstract The curative Graft-versus-Leukemia (GvL) effect of allogeneic stem cell transplantation (SCT) and Donor Lymphocyte Infusions (DLI) is frequently complicated by Graft-versus-Host Disease (GvHD). To date, it is not possible to prevent GvHD without sacrificing the GvL effect. Recently, in a number of murine transplantation studies, administration of naturally occurring CD4+CD25+ regulatory T (Treg) cells in recipients of allogeneic bone marrow effectively prevented GvHD without abrogating GvL. If human (hu)CD4+CD25+ Treg cells also possess such properties, they may become new cellular immunotherapeutics for the prevention of GvHD. Therefore, we have started to investigate the impact of huTreg cells on GvHD in a recently developed, highly relevant xenogeneic(x)-GvHD model in immunodeficient Rag2−/− γc−/− mice. This model represents several features of human allo-GvHD, such as the involvement of both CD4 and CD8 T cells, the association of GvHD with a “cytokine storm” of several Th1/Th2 and inflammatory cytokines and the similarity of skin histopathology to the human allo-GvHD(1). As in this model the x-GvHD is induced by the i.v. injection of huPBMC and the severity of x-GvHD correlates with the number of T cells in the administered PBMC, we explored the impact of Treg cells on x-GvHD either by depletion of Treg cells from huPBMC at different administration doses of effector T cells (4-15 x106 CD25− T cells) and or co-injection of autologous Treg cells at high doses of effector T cells (12-15 x106 T cells). PBMC were isolated from the buffycoats of healthy blood bank donors. Part of the PBMC was used as effector cells, the remaining cells were fractionated into CD25+ and CD25− subsets, which contain Treg cells and conventional T cells, respectively. Different groups of mice were injected with low to high doses of Treg-cell-depleted-PBMC or with high doses PBMC supplemented with 4-6 x106 Treg cell-enriched CD25+ cells. Control mice received equivalent numbers of unmodified PBMC only. The development of x-GvHD was monitored weekly by determination of body weight, clinical scores (ruffled fur, alopecia, mobility) and survival. Peripheral blood obtained from orbital vein was analyzed for human T cell engraftment and expansion. In three independent experiments, depletion of Treg cells significantly exacerbated the x-GvHD signs and lethality. In striking contrast, the development of x-GvHD was significantly inhibited by the co-injection of Treg cell enriched cell fractions. In two independent experiments Treg cells completely protected mice from lethal x-GvHD. Phenotypical analyses of peripheral blood revealed that addition of Treg cells did not disturb huT cell engraftment, but inhibited the expansion of huT cells between 3-5 weeks of administration. These results demonstrate the effective control of x-GvHD in Rag2−/− γc−/− mice by huTreg cells. Studies are underway to reveal the mechanism of GvHD inhibition and the impact of huTreg cells on GvL. (1) R.S. van Rijn, E.R. Simonetti, M.C.H. Hogenes, G. Storm, A. Hagenbeek, H. Spits, K. Weijer, A. C. M. Martens, and S.B. Ebeling. A new in vivo model for graft-versus-host disease by intravenous transfer of human peripheral blood mononuclear cells in RAG2−/− γc−/− double mutant mice.

R404 – Regulatory T Cells and Clinical Outcome in HNSCC Patients

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P178-P178
Author(s):  
Osama Alhamarneh ◽  
Nicholas D. Stafford ◽  
John Greenman
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Clinical Outcome ◽  
Treg Cell ◽  
Cell Population ◽  
Peripheral Blood ◽  
Treg Cells ◽  
Clinicopathological Parameters ◽  
Pre Treatment ◽  
Disease Stages

Problem To determine the correlation between peripheral blood CD4+CD25high regulatory T cells (Treg), a suppressor cell population that dampen the immune response, and clinical outcome and survival in HNSCC patients. Methods Treg cell numbers in the peripheral blood of newly-presenting, untreated HNSCC patients (n=65) were determined pre-operatively, 4–6 weeks after treatment (n=30) and in a cohort of healthy controls (n=35) of similar age and sex, after Treg cell isolation using magnetic microbeads (Miltenyi Biotec) by flow cytometry. The Mann-Whitney U test was used to analyse the correlations between Treg cell levels and clinical outcome. Results Treg cells were significantly higher in patients pre-operatively vs. controls (p=0.002). After treatment, patients showed a significant rise compared with their pre-treatment levels (p=0.022). Pre-treatment Treg cells levels did not correlate with survival or any of the other conventional clinicopathological parameters. However, higher Treg cells levels were discovered in the advanced disease stages (III/IV vs. I/II, median 6.3 vs 4.3) in the pre-treatment group that turned into significantly higher levels in the early disease stages post treatment (I/II vs. III/IV, median 10.8 vs. 5.67 p=0.044). Conclusion Although peripheral blood Treg cells levels were higher in patients when compared to controls, no correlation was found between this cell population and clinical outcome or survival. In contrast with gastric, colorectal and ovarian tumors, Treg cell levels did not normalize 4–6 weeks after curative treatment in this cohort of HNSCC patients. Studies into Treg cell function are thus required to try and elucidate the apparent paradox in Treg cell levels observed in HNSCC. Significance The presence of Regulatory T cells in the peripheral blood of HNSCC patients may be detrimental to host defence against tumor. Further studies are needed to explore their role in the tumor microenvironment and their correlation with clinical outcome.

Elevated Expression of IL-17 and IL-23 in Patients with Immune Thrombocytopenic Purpura

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4537-4537
Author(s):  
Feng Li ◽  
Shanhua Zou ◽  
Yunfeng Cheng
Keyword(s):  
T Cells ◽  
Immune Thrombocytopenic Purpura ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Statistical Difference ◽  
Plasma Concentrations ◽  
Healthy Controls ◽  
Cd4 Cells ◽  
Thrombocytopenic Purpura ◽  
Ifn Γ

Abstract Introduction: In conjunction with IL-6 and TGF-β, IL-23 stimulates naïve CD4+ T cells to differentiate into Th17 cells. Th17 cells produce IL-17, a pro-inflammatory cytokine that play an important role in the pathogenesis of several autoimmune disorders. However, to date, the role of Th17 cells in immune thrombocytopenic purpura (ITP), a type of autoimmune diseases, has not been clearly established yet. Methods: Peripheral bloods were obtained from 10 patients with ITP at onset, in remission and from 15 healthy control subjects. The frequencies of IL-17 producing T cells in peripheral blood were analyzed by flow cytometry. Peripheral blood Mononuclear cells (PBMCs) were isolated using Ficoll density-gradient centrifugation and the CD4+ cells were separated by immuno-magnetic microbeads selection. Plasma concentrations of Th17 cell-associated cytokines such as IL-12, IL-17, IL-23, IFN-γ, IL-6 and TGF-β were measured using ELISA. The mRNA expression levels of IL-17, IL-12p40, IFN-γ, IL-23p19 in CD4+ cells were determined by Real-Time PCR. Results: The frequencies of IL-17-producing T cells were significantly increased in ITP patients at onset, compared to ITP patients in remission (10.7±5.5 % vs 4.1±3.5 %, p &lt; 0.05) and healthy controls (10.7±5.5 % vs 2.1±1.6 %, p &lt; 0.05), however there was no statistical difference between ITP patients in remission and healthy controls. Comparing to healthy subjects, the plasma concentrations of IL-12 (33.3±15.25 pg/ ml vs 12.8±7.24 pg/ml, p&lt;0.05), IL-17 (37.3±12.1 pg/ml vs 5.1±3.6 pg/ml, p &lt; 0.05), IL-23 (30.01±9.33 pg/ml vs 10.42±13.19 pg/ml, p &lt; 0.05) in patients with ITP at onset were found significantly elevated whereas no statistical difference was observed for the levels of IL-12, IL-17 and IL-23 between ITP patients in remission and healthy controls. Furthermore, the expression levels of IL-23p19 mRNA were significantly increased in ITP patients at onset, compared to healthy controls. Changes in IL-23p19 mRNA expression and IL-17 were strongly correlated (R = 0.66, p &lt; 0.05). Conclusion: Our results support the hypothesis that Th17 cells are involved in the development of ITP and Th17 cells could potentially constitute a novel therapeutic target.

scholarly journals Transcriptional Control of Regulatory T Cells in Cancer: Toward Therapeutic Targeting?

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3194
Author(s):  
Pierre Stéphan ◽  
Raphaëlle Lautraite ◽  
Allison Voisin ◽  
Yenkel Grinberg-Bleyer
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Treg Cell ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Treg Cells ◽  
Multiple Strategies ◽  
Cell Transcriptome ◽  
And Function ◽  
Novel Therapeutic

Extensive research in the past decades has highlighted the tight link between immunity and cancer, leading to the development of immunotherapies that have revolutionized cancer care. However, only a fraction of patients display durable responses to these treatments, and a deeper understanding of the cellular and mechanisms orchestrating immune responses to tumors is mandatory for the discovery of novel therapeutic targets. Among the most scrutinized immune cells, Forkhead Box Protein P3 (Foxp3)+ Regulatory T cells (Treg cells) are central inhibitors of protective anti-tumor immunity. These tumor-promoting functions render Treg cells attractive immunotherapy targets, and multiple strategies are being developed to inhibit their recruitment, survival, and function in the tumor microenvironment. In this context, it is critical to decipher the complex and multi-layered molecular mechanisms that shape and stabilize the Treg cell transcriptome. Here, we provide a global view of the transcription factors, and their upstream signaling pathways, involved in the programming of Treg cell homeostasis and functions in cancer. We also evaluate the feasibility and safety of novel therapeutic approaches aiming at targeting specific transcriptional regulators.

scholarly journals Changes in the Peripheral Blood Treg Cell Proportion in Hepatocellular Carcinoma Patients After Transarterial Chemoembolization With Microparticles

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhizhong Ren ◽  
Yuanxun Yue ◽  
Yuewei Zhang ◽  
Jiahong Dong ◽  
Ying Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Immune Function ◽  
Treg Cell ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Transarterial Chemoembolization ◽  
Treg Cells ◽  
Regulatory Effect ◽  
Cell Proportion

ObjectiveTransarterial chemoembolization (TACE) stands for an ideal therapy for patients with intermediate stage HCC. This study was carried out to observe the effect of microparticles-transarterial chemoembolization (microparticles-TACE, m-TACE) on the immune function of hepatocellular carcinoma (HCC) patients by detecting the proportion of regulatory (Treg) cells in the peripheral blood of HCC patients before and after m-TACE, and to determine whether m-TACE has a positive regulatory effect on the immune function of HCC patients.Methods33 HCC patients treated with Gelatn Sponge Microparticles (GSMs-TACE) were enrolled. Flow cytometry was used to determine the proportion of Treg cells and CD4+/CD8+ T cells in peripheral blood of HCC patients 1 day before GSMs-TACE, 1 to 2 weeks and 3 to 5 weeks after GSMs-TACE, respectively.ResultsThe Tregs cell proportion of HCC patients was significantly higher than that of the healthy and cirrhosis controls and was associated with various clinical indicators of HCC patients. The Treg cell proportion in HCC patients with BCLC stage C was higher than that of stage B patients; The Treg cell proportion at 1 to 2 weeks postoperatively was 8.54 ± 1.27%, which was significantly lower than that before the GSMs-TACE. The Treg cell proportion at 3 to 5 weeks postoperatively was 7.59 ± 1.27%, which continued to decline. The ratio of CD4+/CD8+ T cells was 1.31 ± 0.56, 1.86 ± 0.73, 1.76 ± 0.58% (P&lt;0.01) respectively.ConclusionThese results indicated that m-TACE could exert a positive regulatory effect on the anticancer immune function of HCC patients, which may be used in combination with immune adjuvant therapies to enhance the efficacy of HCC.

Immunodominant epitopes on glycoprotein IIb-IIIa recognized by autoreactive T cells in patients with immune thrombocytopenic purpura

Blood ◽  
2001 ◽  
Vol 98 (1) ◽  
pp. 130-139 ◽  
Author(s):  
Masataka Kuwana ◽  
Junichi Kaburaki ◽  
Hidero Kitasato ◽  
Miyako Kato ◽  
Shinichi Kawai ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Thrombocytopenic Purpura ◽  
Peripheral Blood ◽  
Thrombocytopenic Purpura ◽  
Amino Terminal ◽  
Healthy Donors ◽  
T Cell Lines ◽  
Immunodominant Epitopes

Abstract It was recently reported that autoreactive CD4+ T cells to glycoprotein IIb-IIIa (GPIIb-IIIa) mediate antiplatelet autoantibody production in patients with immune thrombocytopenic purpura (ITP). To further examine the antigenic specificity of the GPIIb-IIIa–reactive T cells, 6 recombinant fragments encoding different portions of GPIIbα or GPIIIa were generated and tested for their ability to stimulate antigen-specific T-cell proliferation and anti–GPIIb-IIIa antibody production in vitro. T cells from the peripheral blood of 25 patients with ITP and 10 healthy donors proliferated in response to recombinant GPIIb-IIIa fragments in various combinations. The amino-terminal portions of both GPIIbα and GPIIIa (IIbα18-259 and IIIa22-262) were frequently recognized (60% and 64%, respectively) compared with other fragments (4%-28%) in patients with ITP, but this tendency was not detected in healthy donors. In subsequent analyses in patients with ITP, T-cell reactivities to IIbα18-259 and IIIa22-262 were consistently detected, whereas those to other fragments were sometimes lost. In vitro antigenic stimulation of peripheral blood mononuclear cells with IIbα18-259 or IIIa22-262 promoted the synthesis of anti–GPIIb-IIIa antibodies in patients with ITP, but not in healthy donors. Of 15 CD4+ T-cell lines specific for platelet-derived GPIIb-IIIa generated from 5 patients with ITP, 13 lines recognized IIbα18-259, IIIa22-262, or both. T-cell lines reactive to IIbα18-259 or IIIa22-262 promoted the production of anti–GPIIb-IIIa antibodies that were capable of binding to normal platelet surfaces. These results indicate that the immunodominant epitopes recognized by pathogenic CD4+ T cells in patients with ITP are located within the amino-terminal portions of both GPIIbα and GPIIIa.

scholarly journals Function of regulatory T-cells improved by dexamethasone in Graves' disease

2012 ◽  
Vol 166 (4) ◽  
pp. 641-646 ◽  
Author(s):  
Yun Hu ◽  
Wei Tian ◽  
Ling-Ling Zhang ◽  
Hao Liu ◽  
Guo-Ping Yin ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Treg Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Treg Cells ◽  
Th2 Cells ◽  
Graves Disease ◽  
Treg Cell Function

ObjectiveIntrathyroid injection of dexamethasone (DEX) has been used to treat Graves' disease (GD); however, the mechanism of this treatment remains poorly understood. The objective of this study was to investigate the effects of DEX on the function of regulatory T (Treg) cells (CD4+CD25+T cells) in patients with GD.MethodsPeripheral blood was obtained from 20 patients with GD, and peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll–Hypaque density gradient separation. CD4+CD25–/CD4+CD25+T cells were isolated by immunomagnetic selection and DEX was co-cultured with PBMCs or isolated T-cells for 72 h. Treg cell function was analyzed using the proliferation rate of CD4+CD25–T cells.ResultsThe proportion of Treg cells and the transcription factor forkhead box P3 (FOXP3) mRNA expression in PBMCs decreased in GD patients compared with healthy subjects, and Treg cell function was impaired in patients with GD. Although the proportion of Treg cells and FOXP3 mRNA expression in PBMCs did not increase, the function of Treg cells improved after the treatment with DEX. Moreover, the proportion of T-helper 2 (Th2) cells was decreased by the DEX treatment.ConclusionsDEX could effectively improve the function of Treg cells and set up a new balance of Th1/Th2 in GD patients. This study might help to further understand the immune mechanism of the intrathyroid injection of DEX in the treatment of GD and facilitate the potential use of this therapy.

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