Changes of Th17 cells, regulatory T cells, Treg/Th17, IL-17 and IL-10 in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

Abstract

Purpose: The aim of this study was to investigate the changes of Helper T cells 17 (Th17 cells), Regulatory T cells (Treg cells), Treg/Th17, Interleukin-17 (IL-17) and Interleukin-10 (IL-10) in patients with type 2 diabetes mellitus (T2DM).

Methods: Four electronic resource databases were searched from their inception to 1 August 2021. Case-control studies about changes of Th17 cells, Treg cells, Treg/Th17, IL-17 and IL-10 in patients with T2DM were retrieved. We performed this meta-analysis via RevMan V.5.3 and Stata14.

Results: 20 studies with 1242 individuals were included in the meta-analysis. Compared with the controls, the patients with T2DM had significantly increased levels of percentage of Th17 cells (SMD, 1.74; 95% CI, 0.47-3.01; p < 0.001), IL-17 (SMD, 2.17; 95% CI, 0.06-4.28; p < 0.001), IL-10 (SMD, 1.20; 95% CI, 0.81-1.59; p = 0.003), but decreased levels of percentage of Treg cells (SMD, -1.17; 95% CI, -2.22 to -0.13; p < 0.001) and Treg/Th17 ratio (SMD, -4.43; 95% CI, -7.07 to -1.78; p < 0.001). Subgroup analysis showed that percentage of CD4⁺CD25⁺FOXP3⁺ Tregs (SMD, -2.36; 95% CI, -3.19 to -1.52; p = 0.003) in patients was notably lower than controls. While not significant changes were found in the percentage of CD4⁺CD25⁺Tregs (SMD, 0.03; 95% CI, -0.34-0.40; p = 0.63) between patients and controls. For plasma or serum IL-10, a higher plasma IL-10 level (SMD,1.37; 95% CI, 0.92-1.82; p = 0.01) was observed in T2DM. While serum IL-10 (SMD, 0.73; 95% CI, 0.35-1.12; p = 0.79) had no obvious difference between patients and controls. For ELISA or flow cytometry, IL-10 (SMD, 1.2; 95% CI, 0.71-1.70; p = 0.001) was higher in T2DM patients by using detection method of ELISA. Yet IL-10 using flow cytometry and subgroup analysis of IL-17 had no significant differences.

Conclusions: Adaptive immune system indeed plays an essential role in the process of T2DM. Imbalance between Th17 and Treg triggers pro-inflammatory environment in patients with T2DM.

Keywords: IL-10; IL-17; Meta-analysis; Regulatory T cells; T2DM; Th17 cells.