OBJECTIVE: Intrathyroid injection of dexamethasone (DEX) has been used to treat Graves' disease (GD); however, the mechanism of this treatment remains poorly understood. The objective of this study was to investigate the effects of DEX on the function of regulatory T (Treg) cells (CD4(+)CD25(+)T cells) in patients with GD. METHODS: Peripheral blood was obtained from 20 patients with GD, and peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque density gradient separation. CD4(+)CD25(-)/CD4(+)CD25(+)T cells were isolated by immunomagnetic selection and DEX was co-cultured with PBMCs or isolated T-cells for 72 h. Treg cell function was analyzed using the proliferation rate of CD4(+)CD25(-)T cells. RESULTS: The proportion of Treg cells and the transcription factor forkhead box P3 (FOXP3) mRNA expression in PBMCs decreased in GD patients compared with healthy subjects, and Treg cell function was impaired in patients with GD. Although the proportion of Treg cells and FOXP3 mRNA expression in PBMCs did not increase, the function of Treg cells improved after the treatment with DEX. Moreover, the proportion of T-helper 2 (Th2) cells was decreased by the DEX treatment. CONCLUSIONS: DEX could effectively improve the function of Treg cells and set up a new balance of Th1/Th2 in GD patients. This study might help to further understand the immune mechanism of the intrathyroid injection of DEX in the treatment of GD and facilitate the potential use of this therapy.
OBJECTIVE: Intrathyroid injection of dexamethasone (DEX) has been used to treat Graves' disease (GD); however, the mechanism of this treatment remains poorly understood. The objective of this study was to investigate the effects of DEX on the function of regulatory T (Treg) cells (CD4(+)CD25(+)T cells) in patients with GD. METHODS: Peripheral blood was obtained from 20 patients with GD, and peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque density gradient separation. CD4(+)CD25(-)/CD4(+)CD25(+)T cells were isolated by immunomagnetic selection and DEX was co-cultured with PBMCs or isolated T-cells for 72 h. Treg cell function was analyzed using the proliferation rate of CD4(+)CD25(-)T cells. RESULTS: The proportion of Treg cells and the transcription factor forkhead box P3 (FOXP3) mRNA expression in PBMCs decreased in GDpatients compared with healthy subjects, and Treg cell function was impaired in patients with GD. Although the proportion of Treg cells and FOXP3 mRNA expression in PBMCs did not increase, the function of Treg cells improved after the treatment with DEX. Moreover, the proportion of T-helper 2 (Th2) cells was decreased by the DEX treatment. CONCLUSIONS:DEX could effectively improve the function of Treg cells and set up a new balance of Th1/Th2 in GDpatients. This study might help to further understand the immune mechanism of the intrathyroid injection of DEX in the treatment of GD and facilitate the potential use of this therapy.
Authors: Bidesh Mahata; Jhuma Pramanik; Louise van der Weyden; Krzysztof Polanski; Gozde Kar; Angela Riedel; Xi Chen; Nuno A Fonseca; Kousik Kundu; Lia S Campos; Edward Ryder; Graham Duddy; Izabela Walczak; Klaus Okkenhaug; David J Adams; Jacqueline D Shields; Sarah A Teichmann Journal: Nat Commun Date: 2020-07-17 Impact factor: 14.919