4.1 Article

Expression of CD4+CD25+Foxp3+Regulatory T Cells, Interleukin 10 and Transforming Growth Factor in Newly Diagnosed Type 2 Diabetic Patients

Journal

Publisher

GEORG THIEME VERLAG KG
DOI: 10.1055/s-0043-113454

Keywords

Newly diagnosed type 2 diabetes; CD4+CD25+Foxp3+regulatory T cells; Insulin resistance; IL-10; TGF-beta

Funding

  1. Science and Technology Department of Jilin Province [20160101035JC]
  2. National Natural Science Foundation of China [81300660]

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Background Recent studies have shown that dysfunction and decrease of regulatory T cells (Tregs) correlates with insulin resistance (IR), one of the most significant mechanisms for type 2 diabetes mellitus (T2DM). To examine potential relationships among Tregs, IR, blood lipid content, and related cytokines, we investigated the frequency of CD4 + CD25 + Foxp3 + Tregs, as well as expression levels of interleukin 10 (IL-10) and transforming growth factor-beta (TGF-beta) in newly diagnosed T2DM patients. Methods Fifty-one newly diagnosed T2DM patients and 55 control individuals were enrolled. According to body mass index (BMI), the T2DM patients were grouped into non-obese and obese groups. Blood was collected in ethylene diamine tetraacetic acid (EDTA) anticoagulant tubes for detection of CD4 + CD25 + Foxp3 + Tregs by flow cytometry. Serum was collected to quantify IL-10 and TGF-beta levels by enzyme-linked immunosorbent assay (ELISA). By comparing percentages of Tregs between non-obese and obese groups, correlation with Treg frequency, homeostasis model assessment of insulin resistance (HOMA-IR), IL-10 and TGF-beta was examined. Results The percentage of CD4 + CD25 + Foxp3 + Tregs in the newly diagnosed T2DM group was significantly lower than in the control group (P < 0.01). Further, levels of IL-10 and TGF-beta were also lower in the T2DM group (P < 0.05). The level of IL-10 was remarkably lower in the obese group than in the non-obese and the control groups (P < 0.01), but there was no significant difference between non-obese group and the control group. The level of TGF-beta was lower in obese group than in the control group (P < 0.05). There was no significant difference between non-obese group and the control group. The frequency of CD4 + CD25 + Foxp3 + Tregs in the obese group was significantly lower than in the non-obese group (P < 0.05). In the obese group, the percentage of Tregs negatively correlated with HOMA-IR and positively correlated with TGF-beta (P < 0.05). There was no obvious correlation between Treg and HOMA-IR in the non-obese group. Conclusion The percentage of CD4 + CD25 + Foxp3 + Tregs and levels of related cytokines IL-10 and TGF-beta were precipitously decreased in newly diagnosed T2DM patients. Therefore, the function of Tregs in limiting the proinflammatory milieu represents an important pathogenic mediator of the development of obesity-induced IR in newly diagnosed T2DM patients. Notably, TGF-beta may play an important role in this process. Thus, enhancing expression of Tregs may improve IR in newly diagnosed T2DM patients with obesity.

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