Changes in T helper cell-related factors in patients with type 2 diabetes mellitus after empagliflozin therapy

Abstract

The immune factors related to T helper (Th) 1 (T-bet, STAT1, and IFN-γ), Th17 (ROR-γt, STAT3, and IL-17), and Treg (FOXP3, STAT5, and IL-10) cells, and SOCS1/3 and the proliferation of Th cells were investigated in type 2 diabetes mellitus patients before (baseline) and after empagliflozin therapy. A total of 56 patients on metformin and gliclazide were separated into two groups: Group 1 did not receive empagliflozin (EMPA^-) and the Group 2 received 10 mg/day of empagliflozin for 6 months (EMPA⁺). The expressions of T-bet, ROR-γt, FOXP3, STAT1/3/5 and SOCS1/3 were evaluated in CD4⁺ T cells with real-time PCR. The production of IFN-γ, IL-17, and IL-10 from CD4⁺ T cells was measured using ELISA. The proliferation of Th cells was assessed with flow cytometry. Six months of empagliflozin therapy significantly reduced the expression of ROR-γt and increased FOXP3 and STAT5 expression, compared to baseline. Production of IL-17 decreased after empagliflozin treatment, while IL-10 was enhanced in the EMPA⁺ group. Oral administration of empagliflozin or the addition of empagliflozin to the cell cultures diminished the proliferation of Th cells. Empagliflozin showed anti-inflammatory effects on Th cells by decreasing Th17-related factors, reducing proliferation capacity, and increasing Treg cell properties.

Keywords: Cytokine; Empagliflozin; T helper cell; Type 2 diabetes mellitus.