Low-dose decitabine modulates myeloid-derived suppressor cell fitness via LKB1 in immune thrombocytopenia
| العنوان: | Low-dose decitabine modulates myeloid-derived suppressor cell fitness via LKB1 in immune thrombocytopenia |
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| المؤلفون: | Xiaofei Ni, Lingjun Wang, Haoyi Wang, Tianshu Yu, Jie Xie, Guosheng Li, Yanfeng Liu, Hai Zhou, Miao Xu, Ming Hou, Jun Peng, Yu Hou |
| المصدر: | Blood. 140:2818-2834 |
| بيانات النشر: | American Society of Hematology, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Mice, Purpura, Thrombocytopenic, Idiopathic, Liver, Myeloid-Derived Suppressor Cells, Immunology, Animals, Mice, SCID, Cell Biology, Hematology, Decitabine, Thrombocytopenia, Biochemistry |
| الوصف: | Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature cells and natural inhibitors of adaptive immunity. Metabolic fitness of MDSCs is fundamental for its suppressive activity toward effector T cells. Our previous studies showed that the number and inhibitory function of MDSCs were impaired in patients with immune thrombocytopenia (ITP) compared with healthy controls. In this study, we analyzed the effects of decitabine on MDSCs from patients with ITP, both in vitro and in vivo. We found that low-dose decitabine promoted the generation of MDSCs and enhanced their aerobic metabolism and immunosuppressive functions. Lower expression of liver kinase 1 (LKB1) was found in MDSCs from patients with ITP, which was corrected by decitabine therapy. LKB1 short hairpin RNA (shRNA) transfection effectively blocked the function of MDSCs and almost offset the enhanced effect of decitabine on impaired MDSCs. Subsequently, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient (SCID) mice to induce ITP in murine models. Passive transfer of decitabine-modulated MDSCs significantly raised platelet counts compared with that of phosphate buffered saline–modulated MDSCs. However, when LKB1 shRNA-transfected MDSCs were transferred into SCID mice, the therapeutic effect of decitabine in alleviating thrombocytopenia was quenched. In conclusion, our study suggests that the impaired aerobic metabolism of MDSCs is involved in the pathogenesis of ITP, and the modulatory effect of decitabine on MDSC metabolism contributes to the improvement of its immunosuppressive function. This provides a possible mechanism for sustained remission elicited by low-dose decitabine in patients with ITP. |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b2d777b0f24cbec36bf434c1b50f78d https://doi.org/10.1182/blood.2022016029 |
| رقم الأكسشن: | edsair.doi.dedup.....7b2d777b0f24cbec36bf434c1b50f78d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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