scholarly journals TET family dioxygenases and the TET activator vitamin C in immune responses and cancer

Blood ◽  
2020 ◽  
Vol 136 (12) ◽  
pp. 1394-1401 ◽  
Author(s):  
Xiaojing Yue ◽  
Anjana Rao
Keyword(s):  
Vitamin C ◽  
Immune Responses ◽  
T Regulatory Cells ◽  
Regulatory Cells ◽  
Loss Of Function ◽  
Hematopoietic Malignancies ◽  
Vitamin C Deficiency ◽  
Tet Proteins ◽  
Epigenetic Regulators

Abstract Vitamin C serves as a cofactor for Fe(II) and 2-oxoglutarate–dependent dioxygenases including TET family enzymes, which catalyze the oxidation of 5-methylcytosine into 5-hydroxymethylcytosine and further oxidize methylcytosines. Loss-of-function mutations in epigenetic regulators such as TET genes are prevalent in hematopoietic malignancies. Vitamin C deficiency is frequently observed in cancer patients. In this review, we discuss the role of vitamin C and TET proteins in cancer, with a focus on hematopoietic malignancies, T regulatory cells, and other immune system cells.

scholarly journals Immune Disorders in Hashimoto’s Thyroiditis: What Do We Know So Far?

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Aleksandra Pyzik ◽  
Ewelina Grywalska ◽  
Beata Matyjaszek-Matuszek ◽  
Jacek Roliński
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
T Regulatory Cells ◽  
Hashimoto Thyroiditis ◽  
Hashimoto's Thyroiditis ◽  
Regulatory Cells ◽  
Review Of Literature ◽  
Immune Disorders ◽  
Cd4 Cells ◽  
Immune Defect

This review of literature attempts to identify the factors that are involved in the pathogenesis of Hashimoto thyroiditis, an immune defect in an individual with genetic susceptibility accompanied with environmental factors. The frequency of Hashimoto’s disease is a growing trend and among Caucasians it is estimated at approximately 5%. The dysfunction of the gland may be clinically evident (0.1–2% of the population) or subclinical (10–15%). The pathology is diagnosed five to ten times more often in women than men and its incidence increases with the age (the peak of the number of cases is between 45 and 65); however, it can also be diagnosed in children. The pathogenesis of Hashimoto’s thyroiditis is still not fully comprehended. In the etiology of Hashimoto thyroiditis excessively stimulated T CD4+ cells are known to play the most important role. Recent research has demonstrated an increasing role of newly discovered cells such as Th17 (CD4+IL-17+) or T regulatory cells (CD4+CD25+highFoxP3+) in the induction of autoimmune disorders. The process of programmed cell death also plays an equally important role in the pathogenesis and the development of hypothyroidism.

scholarly journals Ascorbic acid improves parthenogenetic embryo development through TET proteins in mice

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Wei Gao ◽  
Xianfeng Yu ◽  
Jindong Hao ◽  
Ling Wang ◽  
Minghui Qi ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Embryonic Development ◽  
Real Time Pcr ◽  
Quantitative Real Time Pcr ◽  
Qrt Pcr ◽  
Tet Proteins ◽  
Parthenogenetic Embryo ◽  
Blastocyst Rate

Abstract The TET (Ten-Eleven Translocation) proteins catalyze the oxidation of 5mC (5-methylcytosine) to 5hmC (5-hydroxymethylcytosine) and play crucial roles in embryonic development. Ascorbic acid (Vc, Vitamin C) stimulates the expression of TET proteins, whereas DMOG (dimethyloxallyl glycine) inhibits TET expression. To investigate the role of TET1, TET2, and TET3 in PA (parthenogenetic) embryonic development, Vc and DMOG treatments were administered during early embryonic development. The results showed that Vc treatment increased the blastocyst rate (20.73 ± 0.46 compared with 26.57 ± 0.53%). By contrast, DMOG reduced the blastocyst rate (20.73 ± 0.46 compared with 11.18 ± 0.13%) in PA embryos. qRT-PCR (quantitative real-time PCR) and IF (immunofluorescence) staining results revealed that TET1, TET2, and TET3 expressions were significantly lower in PA embryos compared with normal fertilized (Con) embryos. Our results revealed that Vc stimulated the expression of TET proteins in PA embryos. However, treatment with DMOG significantly inhibited the expression of TET proteins. In addition, 5hmC was increased following treatment with Vc and suppressed by DMOG in PA embryos. Taken together, these results indicate that the expression of TET proteins plays crucial roles mediated by 5hmC in PA embryonic development.

scholarly journals EFFICIENCY OF THE FORMATION OF ANTITUMOR IMMUNE RESPONSES IN THE SYSTEM OF PREVENTIVE VACCINATION OF MICE WITH TESTICULAR ANTIGENS

2021 ◽  
Vol 23 (4) ◽  
pp. 665-670
Author(s):  
A. B. Dorzhieva ◽  
T. S. Khabalova ◽  
Yu. E. Androsova ◽  
E. A. Kaschenko ◽  
I. P. Ivanova ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Cells ◽  
T Regulatory Cells ◽  
Specific Method ◽  
Large Set ◽  
Chemotherapeutic Drugs ◽  
Regulatory Cells ◽  
Biochemical Processes ◽  
Preventive Vaccination ◽  
Experimental Group

Аppearance of a malignant tumor is associated with impaired mechanisms of proliferation, differentiation, apoptosis ability. However, these changes are not enough for immune system to recognize and destroy mutated cells. Weak immunogenicity of tumor-associated antigens (TAA) and the insufficiency of co-stimulating molecules on the surface of tumor cells is a reason for this phenomenon Since biochemical processes of tumor cells and healthy tissue cells are identical, therefore creation of effective chemotherapeutic drugs is limited not by selectivity of their action. So antitumor vaccination is the most effective specific method for both preventing recurrence of a disease and a therapeutic treatment tool in oncology. Xenogeneic proteins are highly immunogenic and effective in breaking immune tolerance to human analogs. In our work, we used sheep testicular AG as a source xenogenic TAAs. Sheep testicles contain a large set of TAAs. Experimental mice were immunized with type liposomal testicular vaccine from sheep, one month after vaccination, to induce tumor growth, cells of carcinoma LLC were implanted in mouse. The life expectancy of the experimental group of mice was 2 times higher compared to the syngenetic control and 20% of them did not develop the tumor at all. In the spleen of mice who did not have tumors after pre-vaccination sheep liposomal testicular AG, T-regulatory cells and T-memory cells were measured. We found a credible decrease in both naive Treg (CD4+CD25+), activated (CD4+CD25+FoxP3+) and both T-memory (CD4+CD44+) and central memory (CD4+CD44+CD62L+) in spleen pre-vaccination mice with compared to the contral intact spleen. Content of IFNg and IL-10 in supernatants of mouse slenocytes derived from vaccinated mice with no tumors was investigated and showed a reliable decrease in the amount of IL-10, but not IFNg. We believe that immunization with xenogenic tumor AGs can lead to the formation of a protective antitumor response. 

scholarly journals Mesenchymal Stem Cells and Myeloid Derived Suppressor Cells: Common Traits in Immune Regulation

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Irina Lyadova Vladimirovna ◽  
Ekaterina Sosunova ◽  
Alexander Nikolaev ◽  
Tatiana Nenasheva
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Responses ◽  
Immune Regulation ◽  
T Regulatory Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Regulatory Cells ◽  
B Regulatory Cells ◽  
Immature Cells

To protect host against immune-mediated damage, immune responses are tightly regulated. The regulation of immune responses is mediated by various populations of mature immune cells, such as T regulatory cells and B regulatory cells, but also by immature cells of different origins. In this review, we discuss regulatory properties and mechanisms whereby two distinct populations of immature cells, mesenchymal stem cells, and myeloid derived suppressor cells mediate immune regulation, focusing on their similarities, discrepancies, and potential clinical applications.

scholarly journals Role of Exosomes in the Regulation of T-cell Mediated Immune Responses and in Autoimmune Disease

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 154 ◽  
Author(s):  
Alberto Anel ◽  
Ana Gallego-Lleyda ◽  
Diego de Miguel ◽  
Javier Naval ◽  
Luis Martínez-Lostao
Keyword(s):  
T Cells ◽  
T Cell ◽  
Autoimmune Disease ◽  
Immune Responses ◽  
T Regulatory Cells ◽  
Inflammatory Diseases ◽  
Activated T Cells ◽  
Regulatory Processes ◽  
Activation Induced Cell Death

: T-cell mediated immune responses should be regulated to avoid the development of autoimmune or chronic inflammatory diseases. Several mechanisms have been described to regulate this process, namely death of overactivated T cells by cytokine deprivation, suppression by T regulatory cells (Treg), induction of expression of immune checkpoint molecules such as CTLA-4 and PD-1, or activation-induced cell death (AICD). In addition, activated T cells release membrane microvesicles called exosomes during these regulatory processes. In this review, we revise the role of exosome secretion in the different pathways of immune regulation described to date and its importance in the prevention or development of autoimmune disease. The expression of membrane-bound death ligands on the surface of exosomes during AICD or the more recently described transfer of miRNA or even DNA inside T-cell exosomes is a molecular mechanism that will be analyzed.

scholarly journals Vitamin C Transporters and Their Implications in Carcinogenesis

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3869
Author(s):  
Kinga Linowiecka ◽  
Marek Foksinski ◽  
Anna A. Brożyna
Keyword(s):  
Vitamin C ◽  
Cancer Biology ◽  
Redox Homeostasis ◽  
Regulation Of Gene Expression ◽  
Dna Demethylation ◽  
Altered Expression ◽  
Tet Proteins ◽  
Active Dna Demethylation ◽  
Hypoxic State

Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the activity of 2-oxoglutarate and Fe2+ dependent dioxygenases (2-OGDD), which are involved in active DNA demethylation (TET proteins), the demethylation of histones, and hypoxia processes. Therefore, vitamin C may be engaged in the regulation of gene expression or in a hypoxic state. Hence, vitamin C has acquired great interest for its plausible effects on cancer treatment. Since its conceptualization, the role of vitamin C in cancer therapy has been a controversial and disputed issue. Vitamin C is transferred to the cells with sodium dependent transporters (SVCTs) and glucose transporters (GLUT). However, it is unknown whether the impaired function of these transporters may lead to carcinogenesis and tumor progression. Notably, previous studies have identified SVCTs’ polymorphisms or their altered expression in some types of cancer. This review discusses the potential effects of vitamin C and the impaired SVCT function in cancers. The variations in vitamin C transporter genes may regulate the active transport of vitamin C, and therefore have an impact on cancer risk, but further studies are needed to thoroughly elucidate their involvement in cancer biology.

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