scholarly journals Elevated Expression of the Long Noncoding RNA MAFTRR in Patients with Hashimoto’s Thyroiditis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Huiyong Peng ◽  
Xiangmei Ding ◽  
Juan Xu ◽  
Yue Han ◽  
Jun Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Roc Curve ◽  
Peripheral Blood ◽  
Hashimoto’S Thyroiditis ◽  
Noncoding Rna ◽  
Hashimoto's Thyroiditis ◽  
Th1 Cells ◽  
Healthy Controls ◽  
Transcript Levels ◽  
Ifn Γ

Background. Long noncoding RNAs (lncRNAs) represent an important novel class of noncoding RNA molecule greater than 200 nucleotides that play a key role in the regulation of autoimmune diseases. Previous studies have demonstrated that MAFTRR (MAF transcriptional regulator RNA) regulated Th1 cells differentiation by inhibiting the expression of MAF in activated CD4+ T cells. However, the effect of MAFTRR on the pathogenesis of Hashimoto’s thyroiditis (HT) remains unclear. This research was aimed at investigating the expression of MAFTRR in Hashimoto’s thyroiditis (HT) as well as the correlation between MAFTRR and Th1 cells. Methods. Thirty-eight HT patients and thirty-eight healthy controls were enrolled in the study. The proportion of Th1 cells and CD8+IFN-γ+ T cells in peripheral blood mononuclear cells (PBMCs) from these specimens was determined by flow cytometric analysis. The transcript levels of MAFTRR, MAF, and IFNG in PBMCs and thyroid glands were detected by quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the potential value of MAFTRR in the HT patients. Results. We found that the proportion of circulating Th1 cells and the transcript levels of IFNG were increased in peripheral blood of the HT patients. The transcript levels of MAFTRR were significantly increased in the HT patients and positively correlated with the percentage of Th1 cells and serum levels of antithyroglobulin antibody and antithyroperoxidase antibody. The transcript levels of MAF, a transcription factor that inhibits Th1 cells activity and IFN-γ production, were attenuated in PBMCs from the HT patients. The transcript levels of IFNG had positive and inverse correlations with MAFTRR and MAF expression in PBMCs from the HT patients, respectively. Additionally, a significantly positive correlation between upregulated MAFTRR expression and augmented IFNG expression was revealed in thyroid tissues from the HT patients. ROC curve suggested that MAFTRR could potentially differentiate the HT patients from healthy controls. Conclusion. MAFTRR is significantly augmented in the HT patients and may contribute to the pathogenic role of the Th1 cells response in HT.

Reduction of Tregs with Expansion of Th1 Cells and Lack of IFN-γ Secretion by GPI Negative T-Cells In PNH

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2240-2240
Author(s):  
Shahram Kordasti ◽  
Modupe Elebute ◽  
Pilar Perez Abellan ◽  
Austin G Kulasekararaj ◽  
Janet Hayden ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
High Resolution ◽  
Peripheral Blood ◽  
Clonal Expansion ◽  
T Cell Subsets ◽  
Th1 Cells ◽  
Healthy Controls ◽  
Significant Difference ◽  
Ifn Γ

Abstract Abstract 2240 Introduction and Aim: Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haematopoietic stem cell disorder characterized by intravascular haemolysis and thrombosis. The pathogenetic link with bone marrow failure syndromes is well recognized, however the process of clonal expansion of the glycosylphosphatidylinositol (GPI)-deficient cells over normal haemotopoiesis remains unclear. To further elucidate mechanisms leading to clonal expansion in PNH, we investigated the immunological profile and performed high-resolution genome-wide karyotyping using Affymetrix SNP6 microarrays. Patients and Methods: The percentage and absolute numbers of CD4+ and CD8+ T-cell subsets, NK cells and B cells in peripheral blood were assessed in 8 patients with PNH prior to any therapy and 8 healthy age matched controls. High resolution SNP6 karyotyping was performed on bone marrow (n=15) and peripheral blood (n=12) of these patients. Bone marrow from an additional 8 patients was enriched for CD34+59- and CD34+59+ cell fractions for SNP array karyotyping. Abberations that overlapped by >50% with variations found in the Database of Genomic Variants, as well as an internal series of 91 normal subjects were excluded from further analysis. T-cells were stimulated and then stained intracellularly for TNF-α and IFN-γ (Th1), IL-4 (Th2) and IL-17 (Th17). NK cells were defined as CD3– CD56+. B cells were defined as CD3-CD19+. CD3+ CD4+ T-cell subsets were defined as CD45RO–CD27+ naïve, CD45RO+ CD27+ CD62L+ central memory, CD45RO+ CD27+ CD62L– effector memory, CD45RO+CD27– effectors and CD45RO–CD27– terminal effectors. CD4+ Tregs were defined as CD3+CD4+ CD25high CD27+Foxp3+. Results: There were no significant differences in the number or percentage of different CD8+ and CD4+ T-cells compared to healthy controls except for the number of Tregs and Th1 cells. In our cohort of patients, the number of Th1 cells was significantly higher than healthy controls (4.1×107/L v 0.93 × 107/L, p=0.039), whereas the number of Tregs cells was lower (0.75 × 107/L v 1.36 × 107/L, p=0.028). There was no significant difference in the number of Th2 and Th17 cells between patient and healthy subjects. Within CD4+ T-cells two distinct CD59+ and CD59- populations were identified, of which the CD59- cells were unable to secrete IFN-γ in response to stimulation compared to CD59+ population. On average 48% of CD4+ CD59+ T-cells secrete IFN-γ compared to 2% in the CD59- population. There was no significant difference in IL17 and IL4 secretion between CD59+ and CD59- T-cells. SNP karyotyping revealed three regions of uniparental disomy (UPD); UPD1p26.11-p34.3, UPD1p13.3-p13.1in one peripheral blood sample and UPD7q32.1-q34 in one bone marrow sample. There were no additional somatic genomic aberrations detected in any of the samples. Of note, purified CD34+59- cells did not reveal any clonal copy number changes or regions of UPD. Conclusion: Specific analysis of Xp22.1 did not reveal any aberrations of the PIGA gene, suggesting aberrations of the PIGA gene may be restricted to mutations or epigenetic abnormalities. Our immunological profiling revealed an expansion of Th1 cells and diminished Tregs in the peripheral blood, which is in contrast to our published data from both MDS and AA patients. The lack of IFN-γ secretion by GPI deficient T-cells also suggests an additional immunological defect in these patients, which may contribute in disease pathogenesis. Disclosures: No relevant conflicts of interest to declare.

Evaluation of Th1/Th2 Lymphocyte Balance in Peripheral Blood Mononuclear Cells of Patients with Hashimoto's Thyroiditis

2020 ◽  
Author(s):  
Hajar VASEGHI ◽  
Fatemeh ESFAHANIAN ◽  
Zohreh JADALI
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
Peripheral Blood Mononuclear Cells ◽  
Hashimoto’S Thyroiditis ◽  
Mononuclear Cells ◽  
Hashimoto's Thyroiditis ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

Background: The role of T cells in the pathogenesis of Hashimoto’s thyroiditis is well established, whereas the precise and likely the overlapping contributions of different T-cell subpopulations to thyroid injury are less understood. The purpose of this study was to assess the expression pattern of two lineage determining transcription factors, T-bet and GATA-3 that regulate differentiation of T cells into Th1 or Th2 cell fates, respectively. Moreover, the mRNA expression and plasma concentration of Th1(IFN-γ) and Th2(IL-4) cytokines were analyzed. Methods: In this case-control study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the expression patterns of various transcripts in 20 patients (in Endocrinology Clinic, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran, in 2015) with Hashimoto’s thyroiditis (HT) and 22 healthy controls. Plasma IL-4 and IFN-γ concentrations were also measured using enzyme-linked immunosorbent assay. Results: T-bet gene expression was significantly lower in patients compared to healthy controls (P=0.014). The expression of IL-4 mRNAs was significantly increased in the peripheral blood mononuclear cells from patients as compared to normal controls (P=0.001). In addition, a marked increase in plasma IL-4 levels were observed in patient group compared to controls (P=0.043). Conclusion: Altered balance between Th1 and Th2 related transcription factors and cytokines may be implicated in the pathogenesis of Hashimoto’s thyroiditis.

LncRNA-ENST00000421645 promotes T cells to secrete IFN-γ by sponging PCM-1 in neurosyphilis

Epigenomics ◽  
2021 ◽  
Author(s):  
Wen-Na Liu ◽  
Kai-Xuan Wu ◽  
Xiao-Tong Wang ◽  
Li-Rong Lin ◽  
Man-Li Tong ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Peripheral Blood ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Chip Assay ◽  
Rna Immunoprecipitation ◽  
Ifn Γ ◽  
Significant Expression

Aim: Neurosyphilis patients exhibited significant expression of long noncoding RNA (lncRNA) in peripheral blood T lymphocytes. In this study, we further clarified the role of lncRNA- ENST00000421645 in the pathogenic mechanism of neurosyphilis. Methods: lncRNA- ENST00000421645 was transfected into Jurkat-E6-1 cells, namely lentivirus (Lv)-1645 cells. RNA pull-down assay, flow cytometry, RT-qPCR, ELISA (Neobioscience Technology Co Ltd, Shenzhen, China) and RNA immunoprecipitation chip assay were used to analyze the function of lncRNA- ENST00000421645. Results: The expression of IFN-γ in Lv-1645 cells was significantly increased compared to that in Jurkat-E6-1 cells stimulated by phorbol-12-myristate-13-acetate (PMA). Then, it was suggested that lncRNA- ENST00000421645 interacts with PCM1 protein. Silencing PCM1 significantly increased the level of IFN-γ in Lv-1645 cells stimulated by PMA. Conclusion: This study revealed that lncRNA- ENST00000421645 mediates the production of IFN-γ by sponging PCM1 protein after PMA stimulation.

scholarly journals Activated but impaired IFN-γ production of mucosal-associated invariant T cells in patients with hepatocellular carcinoma

2021 ◽  
Vol 9 (11) ◽  
pp. e003685
Author(s):  
Wenyong Huang ◽  
Dongmei Ye ◽  
Wenjing He ◽  
Xiaoshun He ◽  
Xiaomin Shi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Peripheral Blood ◽  
Healthy Controls ◽  
Activation Markers ◽  
Mait Cells ◽  
Hla Dr ◽  
Ifn Γ ◽  
And Function

ObjectiveMucosal-associated invariant T (MAIT) cells are innate T cells with immunoregulatory activity and were recently found to be associated with various tumor types. The role of intrasinusoidal MAIT cells in hepatocellular carcinoma (HCC) has not been fully characterized.DesignPeripheral blood samples were obtained from patients with HCC and healthy controls. Liver-associated mononuclear cells (LMCs) were collected from liver perfusions of donors and patients with HCC undergoing liver transplantation. Blood and liver perfusates from patients with HCC were analyzed by flow cytometry for CD3 +CD161+Vα7.2+MAIT cell frequency, phenotype, and function.ResultsThere were fewer MAIT cells in the peripheral blood and liver of patients with HCC than in the healthy controls. Interferon-γ (IFN-γ) production by these cells was also reduced. Peripheral MAIT cells showed upregulation of HLA-DR (Human Leukocyte Antigen DR） and the inhibitory molecule PD-1 (Programmed Cell Death Protein 1), but no significant differences in upregulation were found in intrasinusoidal MAIT cells. MAIT cells were significantly enriched in the liver relative to that in the peripheral blood of patients with HCC. High levels of activation markers and exhaustion markers including HLA-DR, CD69, and PD-1 were observed in LMCs of patients with HCC but not in the peripheral blood. Single-cell RNA sequencing revealed that intrasinusoidal MAIT cells exhibited distinct features in patients with HCC and the controls.ConclusionOur study showed that alterations in MAIT cells are associated with HCC. The distinct activity and function of MAIT cells in the peripheral blood and liver of patients with HCC might suggest a potential role of these cells in disease pathogenesis.

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 < 0.05) and healthy controls (10.7±5.5 % vs 2.1±1.6 %, p < 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<0.05), IL-17 (37.3±12.1 pg/ml vs 5.1±3.6 pg/ml, p < 0.05), IL-23 (30.01±9.33 pg/ml vs 10.42±13.19 pg/ml, p < 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 < 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 Insufficient Phosphorylation of STAT5 in Tregs Inhibits the Expression of BLIMP-1, Leading to a Lack of Tregs in Pediatric Aplastic Anemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2183-2183
Author(s):  
Lifen Huang ◽  
Junbin Huang ◽  
Chengming Zhu ◽  
Hongman Xue ◽  
Chi Kong Li ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Aplastic Anemia ◽  
Inflammatory Cytokines ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Healthy Controls ◽  
Healthy Donors ◽  
Ifn Γ ◽  
Low Expression

Abstract Aplastic anemia (AA) is a group of bone marrow failure diseases characterized by three-line blood cell reduction and decreased myeloproliferation. It is believed that T cell immune disorder is the leading cause of the disease, especially the number and functional damage of regulatory T cells (Tregs). BLIMP-1 is a transcription factor encoded by PRDM1 gene, which is indispensable for Tregs. The expression of BLIMP-1 is mainly induced by the IL-2/STAT5 signaling pathway. However, the level of phosphorylation of STAT5 and the expression of BLIMP-1 in Tregs from patients with AA has not been revealed, and the mechanism of Tregs damage in AA has not yet been clarified. In the present study, we collected peripheral blood from 10 newly diagnosed AA children and 10 age-matched healthy donors. We observed that the ratio of Tregs/lymphocytes and Tregs/CD4 + T cells decreased significantly in AA patients, compared with healthy controls by flow cytometry. In addition, we found significantly elevated levels of inflammatory cytokines IL-2, IL-6, and IFN-γ, but decreased levels of anti-inflammatory cytokines IL-10 and TGF-β in plasma of children with AA, compared with healthy controls. Quantitative real-time PCR showed decreased transcriptional level of BLIMP-1 in peripheral blood mononuclear cells (PBMC) from children with AA, compared with healthy donors. We used flow cytometry to detect the protein level of BLIMP-1 in Tregs and found that the level of BLIMP-1 in Tregs in the peripheral blood of children with AA was significantly lower than that of healthy donors. The correlation analysis showed that the percentage of BLIMP-1 + Tregs was positively correlated with the ratio of Tregs/CD4 + T cells (r=0.829, p＜0.001), the plasma level of IL-10 (r=0.492, p=0.027), and TGF-β (r=0.482, p=0.030), suggesting that low expression level of BLIMP-1 in Tregs may lead to decreased number of Tregs in peripheral blood and declined levels of IL-10 and TGF-β in children with AA. When stimulated IL-2, the level of pSTAT5 in CD4 + T cells of children with AA was significantly reduced compared with that of healthy donors. The level of pSTAT5 in CD4 + T cells was also positively correlated with the ratio of Tregs/CD4 + T cells (r= 0.575, p= 0.008) and the expression of BLIMP-1 in Tregs (r=0.693, p＜0.0001)，suggesting that STAT5 signal is poorly activated in pediatric AA, and it may be an important cause for the low expression of BLIMP-1 in Tregs and the decrease in the number of Tregs in children with AA. Furthermore, we constructed an AA mouse model by co-administering IFN-γ and busulfan for 10 consecutive days. These mice exhibited decreased ratio of Tregs/CD4 +T cells in the spleen and lower BLIMP-1 in Tregs, compared with controls. Also, we isolated Tregs with immunomagnetic beads from spleens of mice and observed that the level of IL-2-stimulated pSTAT5 was lower in isolated Tregs from AA mice than controls. These phenotypes were partially rescued by intervention of IL-2-JES6-1, an antibody complex tends to promote the proliferation of Tregs in mice, while inhibiting the proliferation of effector T cells. IL-2-JES6-1 increased the level of pSTAT5 and the expression of BLIMP-1 in Tregs from spleen of the AA mice, and elevated the ratio of Tregs/CD4 + T cells in the spleen. In conclusion, we found that Tregs from AA patients have impaired phosphorylation of STAT5 and insufficient expression of BLIMP-1, which may contribute to the pathogenesis of AA. Disclosures No relevant conflicts of interest to declare.

scholarly journals Increased Mitochondrial DNA Copy Number and Oxidative Damage in Patients with Hashimoto’s Thyroiditis

2021 ◽  
Author(s):  
Fatemeh Esfahanian ◽  
Mojgan Mirabdolhagh Hazaveh ◽  
Laya Hooshmand Garehbagh ◽  
Kowsar Falahati ◽  
Mitra Ataei ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Oxidative Damage ◽  
Peripheral Blood ◽  
Hashimoto’S Thyroiditis ◽  
Copy Number ◽  
Oxidative Dna Damage ◽  
Hashimoto's Thyroiditis ◽  
Healthy Controls ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number

Background: The purpose of present study was to investigate mitochondrial DNA copy number (mtDNAcn) and mtDNA damage in peripheral blood of patients with Hashimoto's thyroiditis (HT) and healthy controls (HC). Methods: The relative mtDNAcn and oxidative DNA damage in this case-control study were measured in peripheral blood of 50 patients with Hashimoto’s thyroiditis and 50 healthy controls using quantitative real-time PCR. The study was conducted in Tehran University of Medical Sciences hospital, Tehran, Iran in 2018. Results: HT patients had significantly higher mitochondrial DNA copy number and mitochondrial oxidative damage than the comparison group. Conclusion: These data suggest the possible involvement of mitochondria and oxidative stress in the pathophysiology of HT.

scholarly journals Defective Regulatory B Cells Are Associated With Thyroid-Associated Ophthalmopathy

2019 ◽  
Vol 104 (9) ◽  
pp. 4067-4077 ◽  
Author(s):  
Guo Chen ◽  
Yungang Ding ◽  
Qian Li ◽  
Yanbing Li ◽  
Xiaofeng Wen ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Regulatory B Cells ◽  
Peripheral Blood Mononuclear ◽  
Thyroid Associated Ophthalmopathy ◽  
Ifn Γ

Abstract Purpose To investigate the change in IL-10–producing regulatory B cells (Breg), which suppress peripheral immune responses, in patients with thyroid-associated ophthalmopathy (TAO). Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls (n = 54), patients with Graves disease (n = 26), and patients with TAO (N=125), and stimulated with CpG/CD40L. The frequency of IL-10–producing Bregs and the expression of IL-10 in response to TSH stimulation were measured by flow cytometry. CD4+ T cells were cultured with Breg-depleted PBMCs to elucidate the function of Bregs in patients with TAO. The potential immunoregulatory mechanism was also investigated by Western blot and chromatin immunoprecipitation assays. Results Patients with active TAO had higher baseline levels of Bregs in their peripheral blood than both healthy controls and inactive patients. TSH promoted Bregs. Bregs from patients with TAO were defective in suppressing the activation of interferon (IFN)-γ+ and IL-17+ T cells in vitro. Conclusions Regulatory B cells in patients with TAO are functionally defective, suggesting that the defective Bregs might be responsible for the pathogenesis of TAO.

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