scholarly journals Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 939 ◽  
Author(s):  
Shin-ichi Koizumi ◽  
Hiroki Ishikawa
Keyword(s):  
Transcriptional Regulation ◽  
Immune Responses ◽  
T Regulatory Cells ◽  
Treg Cells ◽  
Regulatory Cells ◽  
Peripheral Tissues ◽  
Self Tolerance ◽  
And Function ◽  
And Control ◽  
Secondary Lymphoid Organs

Foxp3-expressing regulatory T (Treg) cells can suppress the activity of various types of immune cells and play key roles in the maintenance of self-tolerance and in the regulation of immune responses against pathogens and tumor cells. Treg cells consist of heterogeneous subsets that have distinct phenotypes and functions. Upon antigen stimulation, naïve-like thymus-derived Treg cells, which circulate in secondary lymphoid organs, can differentiate into effector Treg (eTreg) cells and migrate to and control immune homeostasis of peripheral tissues. eTreg cells are heterogeneous in terms of their ability to localize to specific tissues and suppress particular types of immune responses. Differentiation and function of diverse eTreg subsets are regulated by a variety of transcription factors that are activated by antigens and cytokines. In this article, we review the current understanding of the transcriptional regulation of differentiation and function of eTreg cells.

Generation of T Regulatory Cells in Children with Newly Diagnosed Type 1 Diabetes Mellitus

2011 ◽  
Vol 120 (02) ◽  
pp. 101-109 ◽  
Author(s):  
W. Łuczyński ◽  
N. Wawrusiewicz-Kurylonek ◽  
A. Szypowska ◽  
E. Iłendo ◽  
A. Bossowski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
T Regulatory Cells ◽  
Mrna Level ◽  
Treg Cells ◽  
Newly Diagnosed ◽  
Regulatory Cells ◽  
Proliferation Assays ◽  
And Control

AbstractThere is increasing evidence that T-regulatory (Treg) cells could be used to prevent or cure autoimmune diseases including type 1 diabetes mellitus (T1DM). The aim of the present study was to verify the hypothesis that functional Treg cells can be generated from conventional T-cells separated from a small amount of peripheral blood of children with newly diagnosed T1DM (N=25).CD4+CD25- cells were cultured with Treg expander (CD3/CD28) and IL-2 for generating de novo Treg cells. The assessment of the expression of selected genes and proteins critical to Treg function and the proliferation assays were performed with the use of real-time RT-PCR and flow cytometry.After a 4-week stimulation with Treg expander and IL-2, the percentage of T-regulatory cells was significantly higher compared to the cells treated with medium alone (with no difference between diabetic and control children). However, we found some disturbances in the gene expression at mRNA level for molecules crucial for T-reg function. The induced Tregs from diabetic and control children were fully functional as assessed in proliferation assays.despite some disturbances at mRNA level in the critical gene expression, the suppressive properties of induced Treg cells from diabetic and control children were effective.

scholarly journals The Attenuated Live Yellow Fever Virus 17D Infects the Thymus and Induces Thymic Transcriptional Modifications of Immunomodulatory Genes in C57BL/6 and BALB/C Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-12
Author(s):  
Breno Luiz Melo-Lima ◽  
Danillo Lucas Alves Espósito ◽  
Benedito Antônio Lopes da Fonseca ◽  
Luiz Tadeu Moraes Figueiredo ◽  
Philippe Moreau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Viral Infections ◽  
Yellow Fever Virus ◽  
Treg Cells ◽  
Mhc Class Ib ◽  
Peripheral Tissues ◽  
Thymic Function ◽  
Histocompatibility Complex ◽  
Self Tolerance

Thymus is involved in induction of self-tolerance in T lymphocytes, particularly due to Aire activity. In peripheral tissues, Treg cells and immunomodulatory molecules, like the major histocompatibility complex (MHC) class Ib molecules, are essential for maintenance of autotolerance during immune responses. Viral infections can trigger autoimmunity and modify thymic function, and YFV17D immunization has been associated with the onset of autoimmunity, being contraindicated in patients with thymic disorders. Aiming to study the influence of YFV17D immunization on the transcriptional profiles of immunomodulatory genes in thymus, we evaluated the gene expression ofAIRE, FOXP3, H2-Q7(Qa-2/HLA-G),H2-T23(Qa-1/HLA-E),H2-Q10, andH2-K1following immunization with 10,000 LD50of YFV17D in C57BL/6 and BALB/c mice. The YFV17D virus replicated in thymus and induced the expression ofH2-Q7(Qa-2/HLA-G) andH2-T23(Qa-1/HLA-E) transcripts and repressed the expression ofAIREandFOXP3. Transcriptional expression varied according to tissue and mouse strain analyzed. Expression ofH2-T23(Qa-1/HLA-E) andFOXP3was induced in thymus and liver of C57BL/6 mice, which exhibited defective control of viral load, suggesting a higher susceptibility to YFV17D infection. Since the immunization with YFV17D modulated thymus gene expression in genetically predisposed individuals, the vaccine may be related to the onset of autoimmunity disorders.

scholarly journals CD18 Is Required for Optimal Development and Function of CD4+CD25+ T Regulatory Cells

2005 ◽  
Vol 175 (12) ◽  
pp. 7889-7897 ◽  
Author(s):  
Marissa Marski ◽  
Sravanthi Kandula ◽  
Jerrold R. Turner ◽  
Clara Abraham
Keyword(s):  
T Regulatory Cells ◽  
Regulatory Cells ◽  
Optimal Development ◽  
And Function

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 Antigen-specific Treg cells in immunological tolerance: implications for allergic diseases

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 38 ◽  
Author(s):  
Azza Abdel-Gadir ◽  
Amir H. Massoud ◽  
Talal A. Chatila
Keyword(s):  
Immune Responses ◽  
Treg Cell ◽  
Allergic Diseases ◽  
Treg Cells ◽  
Immunological Tolerance ◽  
Inflammatory Disorders ◽  
Cell Responses ◽  
Recent Advances ◽  
And Function ◽  
Is Failure

Allergic diseases are chronic inflammatory disorders in which there is failure to mount effective tolerogenic immune responses to inciting allergens. The alarming rise in the prevalence of allergic diseases in recent decades has spurred investigations to elucidate the mechanisms of breakdown in tolerance in these disorders and means of restoring it. Tolerance to allergens is critically dependent on the generation of allergen-specific regulatory T (Treg) cells, which mediate a state of sustained non-responsiveness to the offending allergen. In this review, we summarize recent advances in our understanding of mechanisms governing the generation and function of allergen-specific Treg cells and their subversion in allergic diseases. We will also outline approaches to harness allergen-specific Treg cell responses to restore tolerance in these disorders.

Dexamethasone affects day/night development and function of thymus-derived T regulatory cells

Immunobiology ◽  
2019 ◽  
Vol 224 (5) ◽  
pp. 614-624
Author(s):  
Ewelina Kiernozek ◽  
Anna Bieńkowska ◽  
Magdalena Markowska ◽  
Ewa Kozlowska ◽  
Nadzieja Drela
Keyword(s):  
T Regulatory Cells ◽  
Regulatory Cells ◽  
And Function

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 Recent advances with Treg depleting fusion protein toxins for cancer immunotherapy

Immunotherapy ◽  
2019 ◽  
Vol 11 (13) ◽  
pp. 1117-1128 ◽  
Author(s):  
Pankaj Kumar ◽  
Amit Kumar ◽  
Sadiya Parveen ◽  
John R Murphy ◽  
William Bishai
Keyword(s):  
Diphtheria Toxin ◽  
Antitumor Immunity ◽  
T Regulatory Cells ◽  
Treg Cells ◽  
Clinical Development ◽  
Bacterial Toxins ◽  
Regulatory Cells ◽  
Protein Toxins ◽  
Cancer Immunotherapies ◽  
Pseudomonas Aeruginosa Exotoxin

T regulatory cells (Tregs) are an important T cell population for immune tolerance, prevention of autoimmune diseases and inhibition of antitumor immunity. The tumor-promoting role played by Tregs in cancer has prompted numerous approaches to develop immunotherapeutics targeting Tregs. One approach to depletion of Treg cells is retargeting the highly potent cytotoxic activity of bacterial toxins. These agents capitalize on the well-characterized bacterial toxins, diphtheria toxin and Pseudomonas aeruginosa exotoxin A–both of which harbor membrane translocation domains and enzymatic domains that catalytically halt protein synthesis within intoxicated eukaryotic cells and act at picomolar or subpicomolar concentrations. In this review, we summarize the preclinical and clinical development of several Treg-depleting cancer immunotherapies based on these two bacterial toxins.

scholarly journals Pertussis toxin as an adjuvant suppresses the number and function of CD4+CD25+ T regulatory cells

2006 ◽  
Vol 36 (3) ◽  
pp. 671-680 ◽  
Author(s):  
Xin Chen ◽  
Robin T. Winkler-Pickett ◽  
Nicholas H. Carbonetti ◽  
John R. Ortaldo ◽  
Joost J. Oppenheim ◽  
...  
Keyword(s):  
Pertussis Toxin ◽  
T Regulatory Cells ◽  
Regulatory Cells ◽  
And Function

scholarly journals Runx1 and Runx3 Are Involved in the Generation and Function of Highly Suppressive IL-17-Producing T Regulatory Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e45115 ◽  
Author(s):  
Lequn Li ◽  
Nikolaos Patsoukis ◽  
Victoria Petkova ◽  
Vassiliki A. Boussiotis
Keyword(s):  
T Regulatory Cells ◽  
Regulatory Cells ◽  
And Function
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