Identification of key genes implicated in the suppressive function of human FOXP3+CD25+CD4+ regulatory T cells through the analysis of time‑series data

Bai, Xiaofeng; Shi, Hua; Yang, Mingxi; Wang, Yuanlin; Sun, Zhaolin; Xu, Shuxiong

doi:10.3892/mmr.2017.8366

Cited by 4 publications

(3 citation statements)

References 52 publications

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“…During acute viral infections, regulatory T lymphocytes (Tregs), a subpopulation of T cells (FoxP3 + CD4 + CD25 + ), play an essential role in controlling inflammation and preventing autoimmunity and tissue complications by regulating immune system homeostasis. Human FOXP3 + cluster of differentiation (CD)25 + CD4 + Tregs are a type of T cells that express CD4, CD25 and FOXP3, which are critical for maintaining immune homeostasis [ 170 ].…”

Section: Discussionmentioning

confidence: 99%

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

Ailioaie

Litscher

et al. 2022

IJMS

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Celiac disease (CD) comprises over 1% of the world’s population and is a chronic multisystem immune-mediated condition manifested by digestive and/or extradigestive symptoms caused by food intake of gluten. This review looked at the risk of children diagnosed with CD developing SARS-CoV-2 infection and possible severe forms of COVID-19. A better understanding of the interaction and effects of SARS-CoV-2 infection in CD is very important, as is the role of environmental and genetic factors, but especially the molecular mechanisms involved in modulating intestinal permeability with impact on autoimmunity. CD inspired the testing of a zonulin antagonist for the fulminant form of multisystem inflammatory syndrome in children (MIS-C) and paved the way for the discovery of new molecules to regulate the small intestine barrier function and immune responses. Original published works on COVID-19 and CD, new data and points of view have been analyzed because this dangerous virus SARS-CoV-2 is still here and yet influencing our lives. Medical science continues to focus on all uncertainties triggered by SARS-CoV-2 infection and its consequences, including in CD. Although the COVID-19 pandemic seems to be gradually extinguishing, there is a wealth of information and knowledge gained over the last two years and important life lessons to analyze, as well as relevant conclusions to be drawn to deal with future pandemics. Zonulin is being studied extensively in immunoengineering as an adjuvant to improving the absorption of new drugs and oral vaccines.

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Section: Discussionmentioning

confidence: 99%

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

Ailioaie

Litscher

et al. 2022

IJMS

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“…Tregs express numerous receptors and non-receptor molecules on their surface that can be used as hallmarks to identify these cells. These markers include CD4 (one of the first markers expressed by Tregs), CD25 (essential for Tregs differentiation), and Forkhead box P3 (FOXP3) transcription factor (required for Tregs development and suppressive activity) [ 23 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

Toward finding the difference between untreated celiac disease and COVID-19 infected patients in terms of CD4, CD25 (IL-2 Rα), FOXP3 and IL-6 expressions as genes affecting immune homeostasis

Asri

Nazemalhosseini‐Mojarad

Mirjalali

et al. 2021

BMC Gastroenterol

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Background Coronavirus disease 2019 (COVID-19) is defined as an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 and celiac disease (CD) is one of the autoimmune multiorgan diseases, which can be accompanied by an increased risk of viral infections. CD patients, especially untreated subjects, may be at greater risk of infections such as viral illnesses. Interleukin (IL)-6, CD4, CD25, and FOXP3 are known as genes affecting immune homeostasis and relate to the inflammation state. This study aimed to compare the expression levels of aforementioned genes in peripheral blood samples of CD and severe COVID-19 patients. Methods Sixty newly diagnosed CD patients with median age (mean ± SD) of 35.40 ± 24.12 years; thirty confirmed severe COVID-19 patients with median age (mean ± SD) of 59.67 ± 17.22, and 60 healthy subjects with median age (mean ± SD) of 35.6 ± 13.02 years; were recruited from March to September 2020. Fresh whole blood samples were collected, total RNA was obtained and cDNA synthesis was carried out. RNA expression levels of IL-6, CD4, CD25, and FOXP3 genes were assessed using real-time quantitative RT-PCR according to the 2−∆∆Ct formula. Statistical analysis was performed using SPSS (V.21) and GraphPad, Prism (V.6). Results While increased expression of CD4, CD25, and FOXP3 was observed in CD patients compared to the control group (p = 0.02, p = 0.03, and p < 0.0001 respectively) and COVID-19 patients group (p < 0.0001 for all of them), their expression levels in COVID-19 patients decreased compared to controls (p < 0.0001, p = 0.01, p = 0.007, respectively). Increased IL-6 expression was observed in both groups of patients compared to controls (p < 0.0001 for both of them). Conclusions Although untreated CD patients may be at greater risk of developing into severe COVID-19 if they are infected by SARS-CoV-2 virus (due to their high expression of IL-6), increased expression of anti-inflammatory markers in these patients may be beneficial for them with the ability of reducing the severity of COVID-19 disease, which needs to be proven in future studies involving celiac patients infected with COVID-19.

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“…T regs inhibit innate and acquired immune function and can modulate anti-microbial immunity; they also reduce immune damage and maintain immune tolerance. The transcription factor forkhead box P3 (FoxP3) is expressed only in T regs and is a specific marker for this lymphocyte lineage [6].…”

Section: Introductionmentioning

confidence: 99%

Programmed death-1 expression and regulatory T cells increase in the Intestinal mucosa of cytomegalovirus colitis in patients with HIV/AIDS

et al. 2020

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Background: Cytomegalovirus (CMV) is among the most common opportunistic infections identified in patients with HIV/AIDS. CMV often targets the colon in such patients. However, the role of regulatory T cells (T regs) and Programmed death-1 (PD-1) in intestinal CMV infection is unclear. In this study, we evaluate the expression of programmed death-1 (PD-1) and its association with regulatory T cells (T regs) in patients with HIV/AIDS having CMV colitis. Methods: CMV was detected in the intestinal mucosal biopsy samples via nucleic acid in situ hybridization. PD-1, CD4, CD8, and T reg-specific marker as well as the winged-helix transcription factor and forkhead box P3 (FoxP3) were detected by immunohistochemical methods. Results: Intestinal CMV diease was identified in 20 out of 195 patients with HIV/AIDS enrolled in our study. CMV was diagnosed microscopically by the presence of giant cell inclusion bodies in epithelial cells, histiocytes, and fibroblasts. Levels of immunoreactive PD-1 detected in mucosal biopsies from patients with HIV/AIDS having CMV colitis were significantly higher than CMV-negative control group (p = 0.023). FoxP3 + cells were detected in the CMV colitis group slight more than that in the control group. CD4 + T lymphocyte counts in the peripheral blood and intestinal mucosal biopsies from CMV colitis group were all notably decreased compared with those with control group (p < 0.001 for both). PD-1 had a significant negative correlation with CD4 counts in intestinal mucosa (p = 0.016). CD8 + T lymphocyte counts in peripheral blood and intestinal mucosa were slightly lower than those in the control group, although the differences were not statistically significant. Conclusions: CMV colitis with HIV/AIDS is associated with significant changes in T lymphocyte populations. These findings may have important implications for disease pathogenesis and progression.

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Identification of key genes implicated in the suppressive function of human FOXP3+CD25+CD4+ regulatory T cells through the analysis of time‑series data

Cited by 4 publications

References 52 publications

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

Toward finding the difference between untreated celiac disease and COVID-19 infected patients in terms of CD4, CD25 (IL-2 Rα), FOXP3 and IL-6 expressions as genes affecting immune homeostasis

Programmed death-1 expression and regulatory T cells increase in the Intestinal mucosa of cytomegalovirus colitis in patients with HIV/AIDS

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