Down-regulation of Helios Expression in Tregs from Patients with Hypertension

Chen, Zhu-Yue; Chen, Feng; Wang, Yange; Wang, Ding-Hang; Jang, Li-Li; Cheng, Liang

doi:10.1007/s11596-018-1846-9

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…Higher susceptibility of CD31 + Treg to apoptosis could partially explain the lower atheroprotective functions of Tregs in CAD + PWH in our study. In addition, lower expression of FoxP3 and Helios is also observed in patients with hypertension [45]. Our data showing an increase in both recent thymic emigrants and thymic Tregs in PWH with CAD suggests that HIV infection contributes to a higher thymic output of these cells.…”

Section: Discussionsupporting

confidence: 55%

Antiretroviral therapy-treated HIV-infected adults with coronary artery disease are characterized by a distinctive regulatory T-cell signature

Rothan

Yero

Shi

et al. 2021

Aids

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Section: Discussionsupporting

confidence: 55%

Antiretroviral therapy-treated HIV-infected adults with coronary artery disease are characterized by a distinctive regulatory T-cell signature

Rothan

Yero

Shi

et al. 2021

Aids

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“…Decreased levels of Helios+ Tregs have been observed in patients with hypertension and rheumatoid arthritis, with lower expression levels correlating with increased inflammatory markers 84 . Tregs may protect against hypertension by limiting vascular inflammation through suppression of effector T cells 85,86 . Furthermore, our analysis revealed that variants in IZKF2 were disproportionately co-associated with patients with hypertension ( Figure 10).…”

Section: Vascular Inflammation Autophagy and Cardiovascular Dysfunctionmentioning

confidence: 99%

Analysis of Genetic Host Response Risk Factors in Severe COVID-19 Patients

Taylor¹,

Das²,

Pearson³

et al. 2020

Preprint

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BACKGROUND Epidemiological studies indicate that as many as 20% of individuals who test positive for COVID-19 develop severe symptoms that can require hospitalization. These symptoms include low platelet count, severe hypoxia, increased inflammatory cytokines and reduced glomerular filtration rate. Additionally, severe COVID-19 is associated with several chronic co-morbidities, including cardiovascular disease, hypertension and type 2 diabetes mellitus. The identification of genetic risk factors that impact differential host responses to SARS-CoV-2, resulting in the development of severe COVID-19, is important in gaining greater understanding into the biological mechanisms underpinning life-threatening responses to the virus. These insights could be used in the identification of high-risk individuals and for the development of treatment strategies for these patients. METHODS As of June 6, 2020, there were 976 patients who tested positive for COVID-19 and were hospitalized, indicating they had a severe response to SARS-CoV-2. There were however too few patients with a mild form of COVID-19 to use this cohort as our control population. Instead we used similar control criteria to our previous study looking at shared genetic risk factors between severe COVID-19 and sepsis, selecting controls who had not developed sepsis despite having maximum co-morbidity risk and exposure to sepsis-causing pathogens. RESULTS Using a combinatorial (high-order epistasis) analysis approach, we identified 68 protein-coding genes that were highly associated with severe COVID-19. At the time of analysis, nine of these genes have been linked to differential response to SARS-CoV-2. We also found many novel targets that are involved in key biological pathways associated with the development of severe COVID-19, including production of pro-inflammatory cytokines, endothelial cell dysfunction, lipid droplets, neurodegeneration and viral susceptibility factors. CONCLUSION The variants we found in genes relating to immune response pathways and cytokine production cascades, were in equal proportions across all severe COVID-19 patients, regardless of their co-morbidities. This suggests that such variants are not associated with any specific co-morbidity, but are common amongst patients who develop severe COVID-19. Among the 68 severe COVID-19 risk-associated genes, we found several druggable protein targets and pathways. Nine are targeted by drugs that have reached at least Phase I clinical trials, and a further eight have active chemical starting points for novel drug development. Several of these targets were particularly enriched in specific co-morbidities, providing insights into shared pathological mechanisms underlying both the development of severe COVID-19, ARDS and these predisposing co-morbidities. We can use these insights to identify patients who are at greatest risk of contracting severe COVID-19 and develop targeted therapeutic strategies for them, with the aim of improving disease burden and survival rates.

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“…Extensive studies evaluating human Tregs in the context of hypertension are yet to be undertaken. Only one study published in 2018 exists, in which authors reported the down-regulation of Helios + Tregs in hypertensive patients as compared to their normotensive counterparts (60). Additionally, CD4 + T-cells from hypertensive patients have lower FOXP3 mRNA levels than cells from healthy controls (60).…”

Section: The Bidirectional Relationship Between Tregs and Risk Factorsmentioning

confidence: 99%

“…Only one study published in 2018 exists, in which authors reported the down-regulation of Helios + Tregs in hypertensive patients as compared to their normotensive counterparts (60). Additionally, CD4 + T-cells from hypertensive patients have lower FOXP3 mRNA levels than cells from healthy controls (60). This data might suggest that the hypertensive microenvironment can negatively impact Tregs populations.…”

Section: The Bidirectional Relationship Between Tregs and Risk Factorsmentioning

confidence: 99%

Getting to the Heart of the Matter: The Role of Regulatory T-Cells (Tregs) in Cardiovascular Disease (CVD) and Atherosclerosis

et al. 2019

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Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. Atherosclerosis is directly associated with CVD and is characterized by slow progressing inflammation which results in the deposition and accumulation of lipids beneath the endothelial layer in conductance and resistance arteries. Both chronic inflammation and disease progression have been associated with several risk factors, including but not limited to smoking, obesity, diabetes, genetic predisposition, hyperlipidemia, and hypertension. Currently, despite increasing incidence and significant expense on the healthcare system in both western and developing countries, there is no curative therapy for atherosclerosis. Instead patients rely on surgical intervention to avoid or revert vessel occlusion, and pharmacological management of the aforementioned risk factors. However, neither of these approaches completely resolve the underlying inflammatory environment which perpetuates the disease, nor do they result in plaque regression. As such, immunomodulation could provide a novel therapeutic option for atherosclerosis; shifting the balance from proatherogenic to athero-protective. Indeed, regulatory T-cells (Tregs), which constitute 5-10% of all CD4+ T lymphocytes in the peripheral blood, have been shown to be athero-protective and could function as new targets in both CVD and atherosclerosis. This review aims to give a comprehensive overview about the roles of Tregs in CVD, focusing on atherosclerosis.

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Down-regulation of Helios Expression in Tregs from Patients with Hypertension

Cited by 5 publications

References 23 publications

Antiretroviral therapy-treated HIV-infected adults with coronary artery disease are characterized by a distinctive regulatory T-cell signature

Antiretroviral therapy-treated HIV-infected adults with coronary artery disease are characterized by a distinctive regulatory T-cell signature

Analysis of Genetic Host Response Risk Factors in Severe COVID-19 Patients

Getting to the Heart of the Matter: The Role of Regulatory T-Cells (Tregs) in Cardiovascular Disease (CVD) and Atherosclerosis

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