Schistosoma japonicum Soluble Egg Antigen Protects Against Type 2 Diabetes in Leprdb/db Mice by Enhancing Regulatory T Cells and Th2 Cytokines

Type 2 diabetes mellitus is associated with an elevated risk of cardiovascular disease, but the mechanism through which diabetes contributes to cardiovascular disease development remains incompletely understood. In this study, we compared the association of circulating regulatory T cells, naïve T cells, effector memory T cells or central memory T cells with cardiovascular disease in patients with and without type 2 diabetes mellitus. Percentage of circulating T cell subsets was analysed by flow cytometry in type 2 diabetes mellitus subjects with and without prevalent cardiovascular disease as well as in non-diabetic subjects with and without prevalent cardiovascular disease from the Malmö SUMMIT cohort. Subjects with type 2 diabetes mellitus had elevated percentages of effector memory T cells (CD4+CD45RO+CD62L–; 21.8% ± 11.2% vs 17.0% ± 9.2% in non-type 2 diabetes mellitus, p < 0.01) and central memory T cells (CD4+CD45RO+CD62L+; 38.0% ± 10.7% vs 36.0% ± 9.5% in non-type 2 diabetes mellitus, p < 0.01). In contrast, the frequency of naïve T cells was reduced (CD4+CD45RO–CD62L+, 35.0% ± 16.5% vs 42.9% ± 14.4% in non-type 2 diabetes mellitus, p < 0.001). The proportion of effector memory T cells was increased in type 2 diabetes mellitus subjects with cardiovascular disease as compared to those without (26.4% ± 11.5% vs 18.4% ± 10.2%, p < 0.05), while no difference in regulatory T cells was observed between these two patient groups. This study identifies effector memory T cells as a potential cellular biomarker for cardiovascular disease among subjects with type 2 diabetes mellitus, suggesting a state of exacerbated immune activation in type 2 diabetes mellitus patients with cardiovascular disease.

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Th17 and regulatory T cells in patients with different time of progression of type 2 diabetes mellitus

Central European Journal of Immunology ◽

10.5114/ceji.2020.94670 ◽

2020 ◽

Vol 45 (1) ◽

pp. 29-36 ◽

Cited By ~ 1

Author(s):

Juan Guzmán-Flores ◽

Joel Ramírez-Emiliano ◽

Victoriano Pérez-Vázquez ◽

Sergio López-Briones

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

T Cells ◽

Type 2 Diabetes Mellitus ◽

Regulatory T Cells

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Effect of Black Tea Consumption on Intracellular Cytokines, Regulatory T Cells and Metabolic Biomarkers in Type 2 Diabetes Patients

Phytotherapy Research ◽

10.1002/ptr.5548 ◽

2015 ◽

Vol 30 (3) ◽

pp. 454-462 ◽

Cited By ~ 16

Author(s):

Fadia Mahmoud ◽

David Haines ◽

Ebaa Al-Ozairi ◽

Ali Dashti

Keyword(s):

Type 2 Diabetes ◽

T Cells ◽

Regulatory T Cells ◽

Black Tea ◽

Tea Consumption ◽

Intracellular Cytokines ◽

Metabolic Biomarkers ◽

Diabetes Patients

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Relationship between Th17 and regulatory T cells in patients with type 2 diabetes mellitus

Frontiers in Immunology ◽

10.3389/conf.fimmu.2015.05.00042 ◽

2015 ◽

Vol 6 ◽

Author(s):

Guzman-Flores Juan ◽

Lopez-Briones Sergio ◽

Pérez-Vázquez Victoriano ◽

Ramírez-De Los Santos Saúl ◽

López-Pulido Edgar

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

T Cells ◽

Type 2 Diabetes Mellitus ◽

Regulatory T Cells

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Changes of Regulatory T Cells and of Proinflammatory and Immunosuppressive Cytokines in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Journal of Diabetes Research ◽

10.1155/2016/3694957 ◽

2016 ◽

Vol 2016 ◽

pp. 1-19 ◽

Cited By ~ 27

Author(s):

Yong-chao Qiao ◽

Jian Shen ◽

Lan He ◽

Xue-zhi Hong ◽

Fang Tian ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

T Cells ◽

Type 2 Diabetes Mellitus ◽

Regulatory T Cells ◽

Transforming Growth Factor ◽

Meta Analysis ◽

Elevated Serum ◽

Serum Levels

Objective. The aim of this study was to investigate the changes of regulatory T cells (Treg), interleukin-6 (IL-6), IL-10, transforming growth factor-β(TGF-β), and tumor necrosis factor-alpha (TNF-α) in patients with type 2 diabetes mellitus (T2DM).Methods. We performed a comprehensive search up to July 2016 for all clinical studies about the changes of Treg, IL-6, IL-10, IL-17, TGF-β, and TNF-αin T2DM patients versus healthy controls.Results. A total of 91 articles (5642 cases and 7378 controls) were included for this meta-analysis. Compared with the controls (allp<0.001), the patients had increased serum levels of IL-6, TGF-β, and TNF-αbut decreased the percentage of peripheral CD4+CD25+Foxp3+Treg and serum IL-10 level. Furthermore, the percentage of peripheral CD4+CD25+Foxp3+Treg (p<0.001) and serum IL-10 level (p=0.033) were significantly lower in the patients with complication and in the patients without complication, respectively. No significant changes about the percentage of CD4+CD25+Treg (p=0.360) and serum IL-17 level (p=0.459) were found in T2DM patients.Conclusions. T2DM patients have decreased the percentage of peripheral CD4+CD25+Foxp3+Treg and levels of serum IL-10 but elevated serum levels of IL-6, TGF-β, and TNF-α. Presence of diabetic complications further lowers the peripheral CD4+CD25+Foxp3+Treg number.

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Immunological Characteristics in Type 2 Diabetes Mellitus Among COVID-19 Patients

Frontiers in Endocrinology ◽

10.3389/fendo.2021.596518 ◽

2021 ◽

Vol 12 ◽

Author(s):

Meifang Han ◽

Ke Ma ◽

Xiaojing Wang ◽

Weiming Yan ◽

Hongwu Wang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

T Cells ◽

Nk Cells ◽

Immune Cells ◽

Diabetic Patients ◽

Th2 Cytokines ◽

Serum Concentrations ◽

Tnf Α

Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT04365634.ContextDiabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear.ObjectiveWe aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients.Design and MethodsIn this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups.ResultsCompared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL‐2R, IL‐6, IL‐8, IL‐10, and TNF‐α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF‐α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8+ T cells and NK cells than survivors.ConclusionThe elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8+ T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.

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Impaired Function of Regulatory T Cells in Type 2 Diabetes Mellitus

Molecular and Cellular Biomedical Sciences ◽

10.21705/mcbs.v4i1.64 ◽

2020 ◽

Vol 4 (1) ◽

pp. 1

Author(s):

Rona Kartika ◽

Heri Wibowo

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

T Cells ◽

Type 2 Diabetes Mellitus ◽

Regulatory T Cells ◽

Inflammatory Response ◽

Treg Cells ◽

Low Grade

Pathogenesis of type 2 Diabetes Mellitus (DM) is often associated with chronic low-grade inflammation. This kind of inflammation is characterized by an increased level of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-1β. From an immunological point of view, an inflammatory response is always followed by an anti-inflammatory response as negative feedback to avoid excessive tissue damages. Regulatory T cells are a subset of cluster of differentiation (CD)4+ T cells that have the function to maintain peripheral tolerance and suppress immune response. This review would discuss the impaired function of regulatory T cells in type 2 DM. DM is a group of metabolic diseases characterized by hyperglycemia due to a defect of insulin secretion or a combination of insulin resistance and relative insulin deficiency. Chronic low-grade inflammation has been known as a key factor in the development of insulin resistance. Regulatory T cells (Treg cells) action through contact and non-contact inhibition could suppress inflammatory response in innate and adaptive immune systems. In type 2 DM, the proportion and function of CD4+CD25+Foxp3+ and CD4+CD25+ regulatory T cell decreases due to the reduced number of Treg cells and the Treg cells depletion contributes to metabolic conditions such as insulin resistance. Moreover, Treg cells are more susceptible to apoptosis, the ability of Treg cells to produce anti-inflammatory cytokines such as transforming growth factor β (TGF-β) and IL-10 decreases, and there is an imbalance between the proportion of Th1/Th17 cells and Treg cells. This inadequate anti-inflammatory response gives rise to the chronic low-grade inflammatory condition in type 2 DM.Keywords: type 2 diabetes mellitus, inflammation, regulatory T cell

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