Department of Hematology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, China.
Department of Hematology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, China;
Allergol Immunopathol (Madr). 2024 Jul 1;52(4):30-37. doi: 10.15586/aei.v52i4.1091. eCollection 2024.
Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a breakdown of immune tolerance; in ITP, the body's immune system mistakenly attacks and destroys platelets. This study aims to investigate the role and underlying mechanisms of in chronic ITP.
Flow cytometry was used to detect the proportion of CD4CD25FOXP regulatory T cells (Tregs) in CD4CD25 T lymphocytes from 20 patients with chronic ITP (CITP), 20 acute ITP (AITP) controls, and 20 healthy individuals.CD4CD25 Treg cells were isolated from peripheral blood of patients with CITP using magnetic beads and then treated with phosphate-buffered saline solution or decitabine (a methylation inhibitor) for 48 h. The levels of interleukin-2 (IL-2), IL-10, and transforming growth factor-beta1 (TGF-β1) in the plasma and CD4CD25 Treg cells were assessed by Enzyme-linked-immunosorbent serologic assay and quantitative real-time polymerase chain reaction (qRT-PCR). FOXP3 level was measured by qRT-PCR and Western blot analysis. Methylation-specific PCR (MS-PCR) was adopted to detect the status of FOXP3 methylation.
The number of Treg cells and the contents of IL-2, IL-10, and TGF-β1 decreased in patients with CITP, compared to the AITP control group and normal group. expression was reduced and methylation increased in patients with CITP, compared to the AITP control group and normal group. Hypermethylation of FOXP3 promoter led to decrease in FOXP3 level in Treg cells. Inhibition of FOXP3 promoter hypermethylation promoted the secretion of IL-2, IL-10, and TGF-β1 in Treg cells.
The number of Treg cells in CITP patients decreased, and the hypermethylation of FOXP3 promoter led to reduction of its expression in Treg cells, thus affecting the immune functioning of Treg cells.
慢性特发性血小板减少性紫癜（ITP）是一种自身免疫性疾病，其特征为免疫耐受的破坏；在 ITP 中，机体的免疫系统错误地攻击并破坏血小板。本研究旨在探讨 在慢性 ITP 中的作用及其潜在机制。
采用流式细胞术检测 20 例慢性 ITP（CITP）患者、20 例急性 ITP（AITP）对照者和 20 名健康个体外周血 CD4+CD25+FOXP3+调节性 T 细胞（Tregs）在 CD4+CD25+T 淋巴细胞中的比例。采用磁珠从 CITP 患者外周血中分离 CD4+CD25+Treg 细胞，并用磷酸盐缓冲液或地西他滨（一种甲基化抑制剂）处理 48 h。采用酶联免疫吸附法和实时定量聚合酶链反应（qRT-PCR）检测血浆和 CD4+CD25+Treg 细胞中白细胞介素-2（IL-2）、白细胞介素-10（IL-10）和转化生长因子-β1（TGF-β1）的水平。采用 qRT-PCR 和 Western blot 分析检测 FOXP3 水平。采用甲基化特异性 PCR（MS-PCR）检测 FOXP3 甲基化状态。
与 AITP 对照组和正常组相比，CITP 患者 Treg 细胞数量减少，IL-2、IL-10 和 TGF-β1 含量降低。与 AITP 对照组和正常组相比，CITP 患者 表达减少，FOXP3 启动子甲基化增加。FOXP3 启动子高甲基化导致 Treg 细胞中 FOXP3 水平降低。抑制 FOXP3 启动子高甲基化促进 Treg 细胞中 IL-2、IL-10 和 TGF-β1 的分泌。
CITP 患者 Treg 细胞数量减少，FOXP3 启动子高甲基化导致 Treg 细胞中 FOXP3 表达减少，从而影响 Treg 细胞的免疫功能。
