Journal of Molecular Medicine

, Volume 90, Issue 2, pp 175–186

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

Original Article

DOI: 10.1007/s00109-011-0816-5

Cite this article as:
Zeng, C., Shi, X., Zhang, B. et al. J Mol Med (2012) 90: 175. doi:10.1007/s00109-011-0816-5

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.

Keywords

Type 2 diabetesCD4+CD25+ T regulatory cellsTh17Th1Immune toleranceHigh-density lipoprotein

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

Supplementary material

109_2011_816_MOESM1_ESM.doc (712 kb)
ESM 1(DOC 712 kb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of SciencesBeijingChina
  2. 2.College of Life Science, Graduate University of Chinese Academy of SciencesBeijingChina
  3. 3.General Hospital of Chinese People’s Armed Police ForcesBeijingChina