title: 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.
authors.affiliation: Department of Hematology, Soochow University Affiliated Children's Hospital, China.
authors.forename: Jianqin
authors.initials: J
authors.lastname: Li
authors.forename: Zhaoyue
authors.initials: Z
authors.lastname: Wang
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Hu
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Lijuan
authors.initials: L
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002469:Cell Separation; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058408:Th1-Th2 Balance / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D003907:Dexamethasone
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