scholarly journals Post-Translational Regulations of Foxp3 in Treg Cells and Their Therapeutic Applications

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Dong ◽  
Cuiping Yang ◽  
Fan Pan
Keyword(s):  
Cell Biology ◽  
Translational Regulation ◽  
Treg Cells ◽  
Peripheral Tolerance ◽  
Forkhead Box P3 ◽  
Therapeutic Applications ◽  
Forkhead Box ◽  
Treg Function ◽  
Considerable Research ◽  
Novel Targets

Regulatory T (Treg) cells are indispensable for immune homeostasis due to their roles in peripheral tolerance. As the master transcription factor of Treg cells, Forkhead box P3 (Foxp3) strongly regulates Treg function and plasticity. Because of this, considerable research efforts have been directed at elucidating the mechanisms controlling Foxp3 and its co-regulators. Such work is not only advancing our understanding on Treg cell biology, but also uncovering novel targets for clinical manipulation in autoimmune diseases, organ transplantation, and tumor therapies. Recently, many studies have explored the post-translational regulation of Foxp3, which have shown that acetylation, phosphorylation, glycosylation, methylation, and ubiquitination are important for determining Foxp3 function and plasticity. Additionally, some of these targets have been implicated to have great therapeutic values. In this review, we will discuss emerging evidence of post-translational regulations on Foxp3 in Treg cells and their exciting therapeutic applications.

scholarly journals Contribution of Regulatory T Cell Methylation Modifications to the Pathogenesis of Allergic Airway Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jiani Li ◽  
Jichao Sha ◽  
Liwei Sun ◽  
Dongdong Zhu ◽  
Cuida Meng
Keyword(s):  
Promoter Region ◽  
Cytosine Methylation ◽  
Allergic Diseases ◽  
Treg Cells ◽  
Epigenetic Modifications ◽  
Food Allergies ◽  
Forkhead Box P3 ◽  
Airway Diseases ◽  
Forkhead Box ◽  
Allergic Disorders

Regulatory T (Treg) cells are a subtype of CD4+ T cells that play a significant role in the protection from autoimmunity and the maintenance of immune tolerance via immune regulation. Epigenetic modifications of Treg cells (i.e., cytosine methylation at the promoter region of the transcription factor, Forkhead Box P3) have been found to be closely associated with allergic diseases, including allergic rhinitis, asthma, and food allergies. In this study, we highlighted the recent evidence on the contribution of epigenetic modifications in Treg cells to the pathogenesis of allergic diseases. Moreover, we also discussed directions for future clinical treatment approaches, with a particular emphasis on Treg cell-targeted therapies for allergic disorders.

scholarly journals Role of regulatory T cells in experimental autoimmune glomerulonephritis

2019 ◽  
Vol 316 (3) ◽  
pp. F572-F581 ◽  
Author(s):  
Stefanie Klinge ◽  
Karsten Yan ◽  
Daniel Reimers ◽  
Karen-Maria Brede ◽  
Joanna Schmid ◽  
...  
Keyword(s):  
T Cells ◽  
Crescentic Glomerulonephritis ◽  
Treg Cells ◽  
Peripheral Tolerance ◽  
Rapid Loss ◽  
Type Iv ◽  
Forkhead Box ◽  
Goodpasture Antigen ◽  
Experimental Autoimmune

Anti-glomerular basement membrane (anti-GBM) disease is characterized by antibodies and T cells directed against the Goodpasture antigen, the noncollagenous domain of the α3-chain of type IV collagen [α3(IV)NC1] of the GBM. Consequences are the deposition of autoantibodies along the GBM and the development of crescentic glomerulonephritis (GN) with rapid loss of renal function. Forkhead box protein P3 (Foxp3)+ regulatory T (Treg) cells are crucial for the maintenance of peripheral tolerance to self-antigens and the prevention of immunopathology. Here, we use the mouse model of experimental autoimmune GN to characterize the role of Treg cells in anti-GBM disease. Immunization of DBA/1 mice with α3(IV)NC1 induced the formation of α3(IV)NC1-specific T cells and antibodies and, after 8–10 wk, the development of crescentic GN. Immunization resulted in increased frequencies of peripheral Treg cells and renal accumulation of these cells in the stage of acute GN. Depletion of Treg cells during immunization led to enhanced generation of α3(IV)NC1-specific antibodies and T cells and to aggravated GN. In contrast, depletion or expansion of the Treg cell population in mice with established autoimmunity had only minor consequences for renal inflammation and did not alter the severity of GN. In conclusion, our results indicate that in anti-GBM disease, Treg cells restrict the induction of autoimmunity against α3(IV)NC1. However, Treg cells are inefficient in preventing crescentic GN after autoimmunity has been established.

scholarly journals Evaluation of IL-17 Producing Memory Regulatory and Effector T Cells Expressing CD26 Molecule in Patients with Psoriasis

2018 ◽  
pp. 453-463
Author(s):  
Behnaz Esmaeili ◽  
Parvin Mansouri ◽  
Alipasha Meysamie ◽  
Maryam Izad
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Treg Cells ◽  
Effector Memory ◽  
Forkhead Box P3 ◽  
Forkhead Box ◽  
Significant Difference ◽  
Cytokine Levels

Memory regulatory T cells (Tregs) has been demonstrated to produce IL-17 in Psoriasis. Forkhead box P3 (Foxp3) has been demonstrated not to be reliable marker to evaluate Treg cells. Effector CD4+T cells also express Foxp3 after activation. Human T helper-17 cells (Th-17) express high level of surface CD26, while regulatory T cells are CD26 negative or low and this phenotype is stable even after activation of Treg cells. In this study, we aimed to analyze IL-17 producing Treg cells using CD26.      Memory T cells were isolated from 10 patients with psoriasis and 10 controls. Ex vivo stimulated IL-17 producing regulatory (Forkhead Box P3 (Foxp3)+CD25+CD26-/low) and effector (Foxp3+CD25+CD26hi) memory T cells were analyzed by flow cytometry. IL-23, IL-6, TNFα, TGFβ and IL-17 cytokine levels were also evaluated. No significant difference in IL-17+memory regulatory T cells was seen between patients and controls (p=0.19). A significant decrease in the percentage of IL-17 producing CD26hi effector memory T cells was observed in patients (p=0.04). However, the percentage of these cells was not different between patients with mild or severe form of psoriasis compared to controls (p=0.13). We could not find any significant difference regarding IL-23, IL-6, TNFα, TGFβ and IL-17 cytokine levels in plasma and cell culture supernatant samples between patients and controls.  Taken together, our results showed a reduced IL-17 producing effector memory CD26hi T cells in patients with psoriasis compared to controls. However, IL-17 producing memory regulatory CD4+T cells of patients showed no significant difference from that of controls

scholarly journals Forkhead Box P3 Methylation and Expression in Men with Obstructive Sleep Apnea

2020 ◽  
Vol 21 (6) ◽  
pp. 2233
Author(s):  
David Sanz-Rubio ◽  
Arianne Sanz ◽  
Luis Varona ◽  
Rosa Bolea ◽  
Marta Forner ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Subclinical Atherosclerosis ◽  
Treg Cells ◽  
Methylation Pattern ◽  
Apnea Hypopnea Index ◽  
Forkhead Box P3 ◽  
Inflammatory Status ◽  
Forkhead Box ◽  
Obstructive Sleep

Background: Epigenetic changes in obstructive sleep apnea (OSA) have been proposed as a mechanism for end-organ vulnerability. In children with OSA, Forkhead Box P3 (FOXP3) DNA methylation were associated with inflammatory biomarkers; however, the methylation pattern and its effect in the expression of this gene have not been tested in adults with OSA. Methods: Plasma samples from subjects without comorbid conditions other than OSA were analyzed (the Epigenetics Status and Subclinical Atherosclerosis in Obstructive Sleep Apnea (EPIOSA) Study: NCT02131610). In 16 patients with severe OSA (Apnea-Hypopnea Index—AHI- > 30 events/h) and seven matched controls (AHI < 5), methylation of FOXP3 gen was evaluated by PCR of the promoter and by pyrosequencing of the intron 1 Treg-specific demethylated region (TSDR). In another 74 patients with OSA (AHI > 10) and 31 controls, we quantified FOXP3 protein expression by ELISA and gene expression by quantitative real-time PCR. C-reactive protein (CRP) and plasma Treg cells were also evaluated. Results: Neither the levels of the promoter nor the TSDR demethylated region were different between controls and patients with OSA, whether they were grouped by normal or high CRP. FOXP3 protein and mRNA expression did not differ between groups. Conclusions: FOXP3 methylation or its expression is not altered in adults with OSA, whatever their inflammatory status.

scholarly journals Potential Application of Tregitopes as Immunomodulating Agents in Multiple Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Wassim Elyaman ◽  
Samia J. Khoury ◽  
David W. Scott ◽  
Anne S. De Groot
Keyword(s):  
Multiple Sclerosis ◽  
Transcription Factor ◽  
Autoimmune Diseases ◽  
Immune Regulation ◽  
Treg Cells ◽  
T Regulatory Cell ◽  
Forkhead Box P3 ◽  
Forkhead Box ◽  
Human Immunoglobulins ◽  
Potential Applications

The induction of immunologic tolerance is an important clinical goal in autoimmunity. CD4+regulatory T (Treg) cells, defined by the expression of the transcription factor forkhead box P3 (FoxP3), play a central role in the control of autoimmune responses. Quantitative and qualitative defects of Tregs have been postulated to contribute to failed immune regulation in multiple sclerosis (MS) and other autoimmune diseases. This paper highlights the potential uses of T regulatory cell epitopes (Tregitopes), natural Treg epitopes found to be contained in human immunoglobulins, as immunomodulating agents in MS. Tregitopes expand Treg cells and induce “adaptive Tregs” resulting in immunosuppression and, therefore, are being considered as a potential therapy for autoimmune diseases. We will compare Tregitopes versus intravenous immunoglobulin (IVIg) in the treatment of EAE with emphasis on the potential applications of Tregitope for the treatment of MS.

A Phenotypic Screening Approach Using Human Treg Cells Identified Regulators of Forkhead Box p3 Expression

2019 ◽  
Vol 14 (3) ◽  
pp. 543-553 ◽  
Author(s):  
Mei Ding ◽  
Johan Brengdahl ◽  
Madelene Lindqvist ◽  
Ulf Gehrmann ◽  
Elke Ericson ◽  
...  
Keyword(s):  
Treg Cells ◽  
Phenotypic Screening ◽  
Forkhead Box P3 ◽  
Forkhead Box ◽  
Screening Approach

scholarly journals ELEVATED METHYLATION LEVELS OF FORKHEAD BOX P3 AS AN INDEPENDENT RISK FACTOR FOR HYPERTENSION

2021 ◽  
Vol 77 (18) ◽  
pp. 1552
Author(s):  
Ling Zhu ◽  
Yin Liu ◽  
Minzhi Ma ◽  
Qianwei Cui ◽  
Yong Zhang ◽  
...  
Keyword(s):  
Risk Factor ◽  
Independent Risk Factor ◽  
Forkhead Box P3 ◽  
Forkhead Box

scholarly journals TCR ligand density and affinity determine peripheral induction of Foxp3 in vivo

2010 ◽  
Vol 207 (8) ◽  
pp. 1701-1711 ◽  
Author(s):  
Rachel A. Gottschalk ◽  
Emily Corse ◽  
James P. Allison
Keyword(s):  
T Cells ◽  
Time Course ◽  
Low Dose ◽  
Cell Receptor ◽  
Peripheral Tolerance ◽  
Ligand Density ◽  
Forkhead Box ◽  
Histocompatibility Complex ◽  
Maximal Induction

T cell receptor (TCR) ligation is required for the extrathymic differentiation of forkhead box p3+ (Foxp3+) regulatory T cells. Several lines of evidence indicate that weak TCR stimulation favors induction of Foxp3 in the periphery; however, it remains to be determined how TCR ligand potency influences this process. We characterized the density and affinity of TCR ligand favorable for Foxp3 induction and found that a low dose of a strong agonist resulted in maximal induction of Foxp3 in vivo. Initial Foxp3 induction by weak agonist peptide could be enhanced by disruption of TCR–peptide major histocompatibility complex (pMHC) interactions or alteration of peptide dose. However, time course experiments revealed that Foxp3-positive cells induced by weak agonist stimulation are deleted, along with their Foxp3-negative counterparts, whereas Foxp3-positive cells induced by low doses of the strong agonist persist. Our results suggest that, together, pMHC ligand potency, density, and duration of TCR interactions define a cumulative quantity of TCR stimulation that determines initial peripheral Foxp3 induction. However, in the persistence of induced Foxp3+ T cells, TCR ligand potency and density are noninterchangeable factors that influence the route to peripheral tolerance.

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