دورية أكاديمية
Low-Dose Decitabine Inhibits Cytotoxic T Lymphocytes-Mediated Platelet Destruction via Modulating PD-1 Methylation in Immune Thrombocytopenia
| العنوان: | Low-Dose Decitabine Inhibits Cytotoxic T Lymphocytes-Mediated Platelet Destruction via Modulating PD-1 Methylation in Immune Thrombocytopenia |
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| المؤلفون: | Panpan Han, Tianshu Yu, Yu Hou, Yajing Zhao, Yang Liu, Yunqi Sun, Haoyi Wang, Pengcheng Xu, Guosheng Li, Tao Sun, Xiang Hu, Xinguang Liu, Lizhen Li, Jun Peng, Hai Zhou, Ming Hou |
| المصدر: | Frontiers in Immunology, Vol 12 (2021) |
| بيانات النشر: | Frontiers Media S.A., 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Immunologic diseases. Allergy |
| مصطلحات موضوعية: | immune thrombocytopenia, decitabine, cytotoxic T lymphocytes, PD-1, PD-L1, Immunologic diseases. Allergy, RC581-607 |
| الوصف: | Cytotoxic T lymphocytes (CTLs)-mediated platelet destruction plays an important role in the pathogenesis of primary immune thrombocytopenia (ITP). The programmed cell death protein 1 (PD-1) signaling can turn off autoreactive T cells and induce peripheral tolerance. Herein, we found that the expression of PD-1 and its ligand PD-L1 on CD8+ T cells from ITP patients was decreased. Activating PD-1 pathway by PD-L1-Fc fusion protein inhibited CTLs-mediated platelet destruction in ITP in vitro. PD-1 promoter hypermethylation in CD8+ T cells was found in ITP patients, resulting in decreased PD-1 expression. The demethylating agent decitabine at a low dose was proved to restore the methylation level and expression of PD-1 on CD8+ T cells and reduce the cytotoxicity of CTLs of ITP patients. The phosphorylation levels of phosphatidylinositol 3-kinase (PI3K) and AKT in CD8+ T cells were significantly downregulated by low-dose decitabine. Furthermore, blocking PD-1 could counteract the effect of low-dose decitabine on CTLs from ITP patients. Therefore, our data suggest that the aberrant PD-1/PD-L1 pathway is involved in the pathophysiology of ITP and enhancing PD-1/PD-L1 signaling is a promising therapeutic approach for ITP management. Our results reveal the immunomodulatory mechanism of low-dose decitabine in ITP by inhibiting CTLs cytotoxicity to autologous platelets through PD-1 pathway. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1664-3224 44049978 |
| Relation: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.630693/full; https://doaj.org/toc/1664-3224 |
| DOI: | 10.3389/fimmu.2021.630693 |
| URL الوصول: | https://doaj.org/article/96e04be14ba4404997894396dc08fcd7 |
| رقم الأكسشن: | edsdoj.96e04be14ba4404997894396dc08fcd7 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 16643224 44049978 |
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| DOI: | 10.3389/fimmu.2021.630693 |