Correction of abnormal T cell subsets by high-dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura

Abstract

Idiopathic thrombocytopenic purpura (ITP) is an acquired autoimmune disorder. Both impaired platelet production and T cell-mediated effects play a role in ITP thrombocytopenia. A Th1 polarization of the immune response, up-regulation of Th17 cells and decreased number of Treg cells have been demonstrated in ITP patients. High-dose dexamethasone was administered as first-line therapy in adult patients with ITP. However, the mechanism of effects of dexamethasone on ITP is still unclear. In this study, we tested the effectiveness of high-dose dexamethasone as initial treatment in adults with immune thrombocytopenic purpura. PBMCs were isolated from Donors, ITP and Treatment groups. T cell subsets were analyzed by FCM and transcriptional factors were checked by Real-time PCR. We found that dexamethasone returned the ratio of Th1/Th2 and the number of Th17 and Treg cells to the normal levels. Furthermore, we identified that dexamethasone corrected the T cell subset levels through inhibiting GATA3 and FOXp3 expression and promoting RORγt expression. Taken together, we reported a previously unrecognized mechanism on dexamethasone in the ITP treatment.

Keywords: Dexamethasone; FCM; FITC; FOXP3; GATA-3; GATA-binding protein 3; IFN-γ; IL2; ITP; Idiopathic thrombocytopenic purpura; PBMCs; PE; PMA; PerCP; RAR-related orphan receptor gamma; RORγ; T cell subset; T help cell 1; T help cell 17; T help cell 2; T-bet; T-box expressed in T cells; Th1; Th17; Th2; Transcription factor; Treg; flow cytometric; fluorescein isothiocyanate; forkhead box P3; idiopathic thrombocytopenic purpura; interferon-γ; interleukin 2; peridin chlorophyll protein; peripheral blood mononuclear cells; phorbol myristate acetate; phycoerythrin; regulatory T cells.