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The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications

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Abstract

Immune disorders are linked to the development of type 2 diabetes (T2D) and its complications. The relationship of CD4+CD25hi T regulatory cells (Treg) and pro-inflammatory Th17 and Th1 subsets in T2D patients with metabolic disorders and complications need to be determined. The ratios of CD4+CD25hi Treg/Th17 cells and CD4+CD25hi Treg/Th1 cells, but not Th17/Th1 cells, were significantly decreased in T2D patients. The thymic output CD4+Foxp3+Helios+ Tregs were normal but peripheral induced CD4+Foxp3+Helios Tregs were decreased in T2D patients. The Bcl-2/Bax ratio decreased in CD4+CD25hi Tregs in T2D patients, supporting the increased sensitivity to cell death of these cells in T2D. CD4+CD25hiCD127 Tregs in T2D patients with microvascular complications were significantly less than T2D patients with macrovascular complications. Importantly, CD4+CD25hiCD127 Tregs were positively correlated with plasma IL-6, whereas IL-17+CD4+cells were negatively related to high-density lipoprotein (HDL). Our data offered evidence for the skewed balance of anti- and pro-inflammatory T cell subsets in T2D patients and identified that HDL closely modulate T cell polarization. These results opened an alternative explanation for the substantial activation of immune cells as well as the development of T2D and complications, which may have significant impacts on the prevention and treatment of T2D patients.

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Abbreviations

CPM:

Counts per minute

FBS:

Fetal bovine serum

FCM:

Flow cytometry

FITC:

Fluorescein isothiocyanate

Foxp3:

Forkhead box P3

Th:

T helper cells

mAbs:

Monoclonal antibodies

MMC:

Mitomycin C

PBMCs:

Peripheral blood mononuclear cells

PE:

Phycoerythrin

PI:

Propidium iodide

Teff:

T effector cells

PMA:

Phorbol-12-myristate-13-acetate

Treg:

T regulatory cells

T2D:

Type 2 diabetes

CTL:

Control

WBC:

White blood cells

HbA1c:

Hemoglobin A1c

HDL:

High-density lipoprotein

LDL:

Low-density lipoprotein

HLA:

Human leucocyte antigen

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Acknowledgments

The authors wish to thank Ms. Jing Wang, Ms. Jianxia Peng, and Mr. Cunsheng Zhang for their expert technical assistance, and Ms. Qinghuan Li for excellent laboratory management. This work was supported by grants from the National Basic Research Program of China (973 program, 2010CB945301, YZ) and the National Natural Science Foundation for Key Project (C30630060, Y.Z.).

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Correspondence to Wenjun Ding or Yong Zhao.

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Chun Zeng, Xiaoyun Shi, and Baojun Zhang contributed equally to this work and thus share the first authorship.

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Zeng, C., Shi, X., Zhang, B. et al. The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications. J Mol Med 90, 175–186 (2012). https://doi.org/10.1007/s00109-011-0816-5

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