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

Abstract

Immune disorders are linked to the development of type 2 diabetes (T2D) and its complications. The relationship of CD4(+)CD25(hi) 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(+)CD25(hi) Treg/Th17 cells and CD4(+)CD25(hi) 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(+)CD25(hi) Tregs in T2D patients, supporting the increased sensitivity to cell death of these cells in T2D. CD4(+)CD25(hi)CD127(-) Tregs in T2D patients with microvascular complications were significantly less than T2D patients with macrovascular complications. Importantly, CD4(+)CD25(hi)CD127(-) 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.