Characterization of IL-17-producing Treg cells in type 2 diabetes patients

The association between type 2 diabetes (T2D) pathogenesis and immune-mediated tissue damage and insulin resistance suggests that T2D patients might benefit from the suppression of pathogenic inflammation. Foxp3⁺ Treg cells are crucial suppressors of inflammation, but the differentiation of Foxp3⁺ Treg cells is not static and is subject to conversion into IL-17-producing Th17-like cells upon receiving external signals. In this study, we examined the production of IL-17 by Treg cells. Compared to non-T2D controls, T2D patients presented significantly higher levels of IL-17-expressing cells in both Foxp3⁻ CD4 T cells and Foxp3⁺ Treg cells. The frequencies of IL-17-nonexpressing Foxp3⁺ Treg cells, on the other hand, were not changed. Interestingly, IL-17-expressing Foxp3⁺ Treg cells were mutually exclusive from IL-10-expressing and TGF-β-expressing Foxp3⁺ Treg cells, suggesting that multiple subpopulations exist within the Foxp3⁺ Treg cells from T2D patients. In T2D patients, the frequencies of IL-17-expressing Foxp3⁺ Treg cells were positively correlated with the body mass index (BMI) and the HbA1c levels of T2D patients. The frequencies of IL-10-expressing Treg cells, on the other hand, were inversely associated with the BMI of both non-T2D controls and T2D patients. In addition, the suppressive activity of Treg cells was significantly lower in T2D patients than in non-T2D controls. Together, our study uncovered a dysregulation in Foxp3⁺ Treg cells from T2D patients, characterized by high IL-17 expression and low suppression activity.