Dexamethasone suppresses the Th17/1 cell polarization in the CD4+ T cells from patients with primary immune thrombocytopenia

Abstract

Introduction: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease with increased Th17 cells in peripheral blood. Th17/1 cells, which were recently characterized as a new differentiated Th17 lineage secreting IL-17 and IFN-γ, play an important role in the pathogenesis of multiple autoimmune diseases. In this study, we investigated whether Th17/1 cells are involved in the pathogenesis of ITP.

Materials and methods: Peripheral blood was obtained from 44 ITP patients and 50 healthy controls. The percentages of T cell subsets were evaluated. We also detected molecular signature of Th17/1 cells in CD4⁺ T cells. Besides, CD4⁺ T cells from ITP patients were treated with dexamethasone, the inhibitor of NF-κB, or rapamycin to evaluate the impact and mechanism of dexamethasone treatment on Th17/1 cells.

Results: We found an elevated percentage and an enhanced specific molecular signature of Th17/1 cells in CD4⁺ T cells in ITP patients. The percentage of Th17/1 cells was correlated positively with Th17 cells in ITP patients and healthy controls. The percentage of Th17/1 cells was correlated with corticosteroid resistance. Dexamethasone reversed the molecular signature of Th17/1 cells and decreased the percentage of Th17/1 cells in vitro. Treatment of dexamethasone and the inhibitor of NF-κB suppressed the phosphorylation of STAT3, while dexamethasone treatment also inhibited the phosphorylation of NF-κB p65.

Conclusions: Our data suggested Th17/1 cells may contribute to the pathogenesis of ITP and dexamethasone could inhibit Th17/1 cells through NF-κB/STAT3 pathway. These results may provide a potential therapeutic strategy of correcting the Th17/1 cell deviation in ITP.

Keywords: Dexamethasone; NF-κB/STAT3 pathway; Primary immune thrombocytopenia; Th17/1 cells.