scholarly journals The Expression of T Cell FOXP3 and T-Bet Is Upregulated in Severe but Not Euthyroid Hashimoto’s Thyroiditis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Stana Tokić ◽  
Mario Štefanić ◽  
Ljubica Glavaš-Obrovac ◽  
Sonja Jaman ◽  
Eva Novosadová ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Hashimoto’S Thyroiditis ◽  
Hormone Replacement ◽  
Study Groups ◽  
Hashimoto's Thyroiditis ◽  
Foxp3 Mrna ◽  
Expression Levels ◽  
Treg Subset ◽  
Mrna Expression Levels

Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disorder characterized by progressive thyroid failure. Th1 and Treg subset of CD4+ cells have been implicated in the pathogenesis; however, less is known about their respective roles across the spectrum of HT clinical presentations. To shed more light on CD4+ subsets role in HT, we investigated the mRNA expression levels of several Th1/Treg-associated transcription factors (T-bet/ETS1, HIF1α/BLIMP1/FOXP3) in peripheral blood T cells of 10 hypothyroid, untreated HT patients, 10 hypothyroid patients undergoing hormone replacement therapy, 12 euthyroid HT subjects, and 11 healthy controls by the qRT-PCR. Compared to euthyroid HT patients and controls, both hypothyroid (2.34-fold difference versus controls, P<0.01) and thyroxine-supplemented patients (2.5-fold, P<0.001) showed an increased FOXP3 mRNA expression in T cells. Similarly, mRNA expression levels of T-bet were upregulated in severely affected but not in euthyroid HT subjects (2.37-fold and 3.2-fold, hypothyroid and thyroxine-supplemented HT patients versus controls, resp., P<0.01). By contrast, no differences in mRNA expression levels of ETS1, BLIMP1, and HIF1α were observed across the study groups. In summary, severe but not euthyroid HT was associated with robust upregulation of T-bet and FOXP3 mRNA in peripheral T cells, independent of the thyroid hormone status but proportional to disease activity.

Immune self-tuning in renal cell carcinoma patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22069-e22069
Author(s):  
A. Busse ◽  
A. Asemissen ◽  
A. Schmittel ◽  
K. Zimmermann ◽  
K. Miller ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Mrna Expression ◽  
Renal Cell ◽  
Performance Status ◽  
Ecog Performance Status ◽  
Foxp3 Mrna ◽  
Expression Levels ◽  
Mrna Expression Levels

e22069 Background: Renal cell carcinoma (RCC) cells can inhibit protective antitumor immunity by secretion of immunosuppressive factors leading to the induction of regulatory T cells. The objective of this study was to investigate the prognostic impact of mRNA expression levels of IL10, TGFβ and forkhead box transcription factor (FoxP3) mRNA in peripheral blood mononuclear cells (PBMCs) of metastatic RCC patients before receiving treatment with sorafenib. Methods: PBMCs of 46 patients were assessed for their expression levels of TGFβ, IL10 and FoxP3 by quantitative RT-PCR. Clinical features considered included ECOG performance status, hemoglobin, alkaline phosphatase, and calcium concentrations. Disease evaluation was performed every 8 weeks following RECIST criteria. Relationship between pre-treatment factors and survival were examined in univariate analyses and subsequently by multivariate analysis using a stepwise Cox regression model. Results: In contrast to FoxP3, mRNA expression levels of IL10 and TGFβ were significantly higher in the 46 RCC patients compared to healthy volunteers: Median expression levels [ratio marker /housekeeping gene PBGD] were 5.56E-05 vs 2.05E-04 (P=0.034) for IL10 and 7.38E-02 vs 3.04E- 01 (P=0.023) for TGFβ. Univariate analysis revealed a negative prognostic influence of IL10 on progression free survival (p=0.04) and on overall survival, although not significant (P= 0.063). Surprisingly, high TGFβ and FoxP3 expression levels had a positive influence on progression free (P<0.001 and P=0.047, respectively) and overall survival (P<0.001 and P= 0.031, respectively). In the multivariate analysis low ECOG performance status and high TGFβ mRNA expression levels were independently associated with worse progression free (P=0.001 and P=0.054,) and worse overall survival (P=0. 006 and P< 0.001, respectively). Conclusions: RCC caused an immune-suppressive phenotype in PBMC characterized by increased mRNA expression levels of IL10 and TGFβ. Surprisingly, in contrast to IL10, a high TGFβ mRNA expression level was an independent good prognostic factor. Whether this observation can be attributed to recently described immune promoting functions of TGFβ needs to be determined. No significant financial relationships to disclose.

scholarly journals TMIC-44. IL-1 ANTAGONIST ANAKINRA INHIBITS GLIOBLASTOMA PROLIFERATION BY ANTAGONIZING THE PROINFLAMMATORY MICROENVIRONMENT

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi257-vi257
Author(s):  
David Effinger ◽  
Max Hübner ◽  
Tingting Wu ◽  
Niklas Thon ◽  
Friedrich-Wilhelm Kreth ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Mrna Expression ◽  
Magnetic Bead ◽  
Cell Phenotype ◽  
Ki 67 ◽  
Expression Levels ◽  
Tumor Environment ◽  
Student’S T ◽  
Mrna Expression Levels

Abstract INTRODUCTION The recombinant IL-1 receptor antagonist anakinra prevents binding of IL-1 to its receptor and blocks IL-1β-mediated proinflammatory signaling. It is currently used in the treatment of autoinflammatory diseases. As inflammation is a major driver of malignancy, we hypothesized that anakinra – by ameliorating the inflammatory tumor environment – might be capable to mitigate glioblastoma (GBM) progression. METHODS T98G GBM cells were cultivated with PBMC, separated by cell culture inserts with or without anakinra and incubated 48h in 5% O2 mimicking the GBM microenvironment. T-cells were obtained by magnetic bead isolation. mRNA expression levels were measured by quantitative Real-Time-PCR (qRT-PCR). Cytokine production was assessed by ELISA. Cell proliferation was analyzed by flow cytometric quantification of Ki-67 protein expression. Anakinra has been provided by Swedish Orphan Biovitrum AB (Sweden). Results are presented as mean±SEM, p-Values were calculated using Student’s t-test. RESULTS After administration of anakinra, mRNA expression levels of the inflammatory and proangiogenic genes IL-1β, COX-2, CCL2 and IL-8 were reduced in T98G (-64%±19.1%, -56.2%±21.3%, -87.1%±28.8%, -91.7%±27.2%, n=7, p< 0.05). Surprisingly, no changes of these targets were detectable in PBMC. However, in T-cells, anakinra induced mRNA expression of Th2 transcription factor GATA3 and the antiinflammatory cytokines IL-4 and IL-10 (+6,7%±4,6%, +36,1%±22,9%, +69,1%32,8%, n=10, p< 0.05). The expression of the protumorigenic genes IL-22, IL-17 as well as IFNγ was dramatically repressed (-63.2%±21.9%, -88.1%±21.7%, -85.6%±45.2%, n=10, p< 0.05), protein secretion of IL-22 and IFNγ was strongly blocked (-36.3%±9.1%, -13.9%±0.5%, n=6, p< 0.05). Importantly, treatment with anakinra markedly attenuated GBM cell proliferation (-20.1%±5%, n=4, p< 0.05). CONCLUSION Anakinra indeed puts the brake on proinflammatory signaling pathways in GBM cells and simultaneously promotes a shift towards an anti-inflammatory T-cell phenotype. As a result, GBM proliferation is diminished. Hence, administration of anakinra might be an interesting and novel therapeutic approach to reduce Glioblastoma aggressiveness.

scholarly journals Current Concepts in Endocrinology for Clinicians and Medical Students. Hashimoto’s Thyroiditis: clinical and subclinical thyroid dysfunction

2018 ◽  
Vol 13 (2) ◽  
pp. 38-42
Author(s):  
Paulo Travassos Neto
Keyword(s):  
T Cells ◽  
Hashimoto’S Thyroiditis ◽  
Genetic Background ◽  
Thyroid Dysfunction ◽  
Cytotoxic T Cells ◽  
Hormone Replacement ◽  
Hashimoto's Thyroiditis ◽  
Thyroid Peroxidase ◽  
Antithyroid Antibody ◽  
Thyroid Hormone Replacement

Hashimoto’s thyroiditis (HT) is an autoimmune and inflammatory disease in which antibodies are directed against the thyroid gland leading to chronic inflammation and hypothyroidism. The autoimmunity against thyroid antigens can be associated to genetic background and environmental factors. Thyroid peroxidase (TPO) and thyroglobulin (TG) are the major autoantigens for characterizing the disease. And the pathogenic mechanism is related to the activation of autoreactive CD4+ T cells, CD8+ cytotoxic T cells and antithyroid antibody producing-B cells. The treatment for hypothyroidism is based on thyroid hormone replacement, the levothyroxine. This review briefly discusses the clinical and pathogenic profile of HT and the importance of a correct diagnostics.

scholarly journals Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Chongli Zhang ◽  
Yong Cui ◽  
Guannan Wang ◽  
Wugan Zhao ◽  
Haiyu Zhao ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
Mrna Expression ◽  
Family Members ◽  
Tumor Grade ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Immune Infiltration ◽  
E2f Transcription Factors ◽  
Mrna Expression Levels

Background. E2F transcription factors is a family of transcription factors, and lots of studies have shown that they play a key role in the occurrence and development of many tumors. However, the association between expression, prognostic value, and immune infiltration in the tumor microenvironment of the eight E2Fs members in ccRCC is still unclear. Methods. We used online databases, such as ONCOMINE, UALCAN, Kaplan–Meier plotter, GEPIA, Metascape, TIMER, and cBioPortal, to analyze the effect of mRNA expression of E2Fs family members in ccRCC on the prognosis of patients and the relationship with immune infiltration. Results. Except for E2F5, other seven members of the family of E2Fs mRNA expression levels in ccRCC tissues were significantly higher than control tissues. And the high expression of E2Fs mRNA in ccRCC patients was related to cancer stage and tumor grade. Survival analysis results suggested that elevated mRNA expression levels of E2F1/2/3/4/7/8 were significantly related to the shorter overall survival (OS) in ccRCC patients ( P  = 3.9E – 06), while high mRNA expression of E2F6 is not related to OS ( P  = 0.061). Mutations of E2Fs were correlated with shorter OS of ccRCC patients ( P  = 7.094E – 5). In addition, mRNA expression of E2F1/2/3/4/7/8 was positively correlated with infiltration of six types of immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions. These results indicate that E2F1/2/3/4/7/8 may be used as a prognostic marker for the survival of ccRCC patients and laid the foundation for studying the immune infiltration role of E2Fs family members in tumors.

scholarly journals Candidate Gene Expression Investigation in Children With Attention Deficit Hyperactivity Disorder

2021 ◽  
Author(s):  
Hilal Akalin ◽  
Yakut Erdem ◽  
Nuriye Gokce ◽  
Sevgi Ozmen ◽  
Muhammet Ensar Dogan ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Mrna Expression ◽  
Attention Deficit ◽  
Study Groups ◽  
Post Treatment ◽  
Control Group ◽  
Expression Levels ◽  
Hyperactivity Disorder ◽  
Pre Treatment ◽  
Mrna Expression Levels

Abstract Background: In this study, expression level analysis of genes associated with Attention Deficit Hyperactivity Disorder (ADHD) (SLC6A3, SLC6A4, SLC1A2, VMAT2, MAOA, COMT, GLYAT, GRM5, DRD4, TPH1, and ADRA2C) by pre-treatment and post-treatment with Atomoxetine and Methylphenidate was investigated. Methods: Forty-three ADHD diagnosed children and 38 healthy children were included to study. Forty-three patients with ADHD were divided into two groups, of which 35 patients used methylphenidate and 8 patients use atomoxetine. Five main study groups were generated: A control group, a group that includes methylphenidate pre-treatment samples, a group includes methylphenidate post-treatment samples, a group that includes atomoxetine pre-treatment samples and a group that includes atomoxetine post-treatment samples. Blood samples (10 ml each) were taken from everyone in study groups into EDTA tubes and RNA isolation was performed. mRNA expression levels of 11 determined candidate genes were showed via reverse transcription quantitative PCR method. Results: The expression levels of SLC6A3 (DAT) of ADHD diagnosed children were significantly higher than the control group, while the mRNA expression levels of SLC6A4, SLC1A2, VMAT2, MAOA, COMT, GLYAT, and TPH1 genes were significantly lower (t- test, p≤0.01).Conclusion: The expression level differences of these genes were determined to be useful as biomarkers in the diagnosis of ADHD. More patient numbers and studies with different groups are needed to fully reveal the relationship between these genes and the disease and its treatment.

scholarly journals The role of CXCR3 and its ligands expression in Brucellar spondylitis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Hu ◽  
Xiaoqian Shang ◽  
Liang Wang ◽  
Jiahui Fan ◽  
Yue Wang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Inflammatory Infiltration ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Inflammatory Damage ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Aim Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. Methods A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. Results In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. Conclusion In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.

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