Abstract TP76: Increased Regulatory T Cells After Treatment of Poly (adp-ribose) Polymerase-1 Inhibitor in Patients With Acute Ischemic Stroke

Abstract

Background: Regulatory T cells (Tregs) have been suggested to have modulatory function of immune response and improve outcome after ischemic stroke. Thus, various strategies to increase Treg in animal model of ischemic stroke have been studied with successful results. The aim of this study is to demonstrate Treg (CD4 + CD25 + FoxP3 + ) proportion in peripheral blood of ischemic stroke patient and the potential effect of poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor on Treg proportion. Methods: Peripheral blood samples were collected from 12 ischemic stroke patients (within 72 hours of stroke onset) and 5 control subjects. Demographics and clinical information were obtained from patients and control subjects. Fluorescence-activate cell sorting (FACS) analyses and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed with peripheral blood mononuclear cells (PBMCs) before and after PARP-1 inhibitor (3-AB, JPI-289 1 μm, JPI-289 10 μm) treatment for 24 hours. Results: Treg proportion was significantly higher in healthy control (3.5 ± 1.8 %) than ischemic stroke patients (1.6 ± 0.6 %) ( p < 0.001). In ischemic stroke patients, regulatory T cell proportion was positively correlated with age (r = 0.595, p = 0.041), but did not show association with infarct volume (r = 0.367, p = 0.241). After PARP-1 inhibitor treatment, the proportion of Treg was increased in high dose (10 μm) JPI-289 group (2.1 ± 0.7 %). However, 3-AB and low dose (1 μm) JPI-289 did not show significant changes of Treg proportion. RT-PCR showed increased expression of Treg associated transcription factors such as FoxP3 and CTLA-4 mRNA after PARP-1 inhibitor treatment. PARP-1 inhibitor treatment also decreased pro-inflammatory cytokines such as IFN-γ, TNF-α, and IL-17 and increased anti-inflammatory cytokines such as IL-4, IL-10, and TGF-β1. Conclusion: Treg proportion was decreased in patient with acute ischemic stroke. However, it was up-regulated after treatment of PARP-1 inhibitors, especially with high dose JPI-289. In addition, PARP-1 inhibitor showed possible anti-inflammatory effect by regulating cytokines. PARP-1 inhibitor may ameliorate outcome of ischemic stroke by immune modulation.