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

The immune factors related to T helper (Th) 1 (T-bet, STAT1, and IFN-gamma), Th17 (ROR-gamma t, 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-gamma t, FOXP3, STAT1/3/5 and SOCS1/3 were evaluated in CD4(+) T cells with real-time PCR. The production of IFN-gamma, 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-gamma t 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. (C) 2021 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Automated summary

The study showed that empagliflozin therapy reduced Th17-related factors, increased Treg cell proliferation, and enhanced Treg cell properties, indicating its anti-inflammatory effects on Th cells.