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首页> 外文期刊>Cellular Physiology and Biochemistry >Heme Oxygenase-1 Restores Impaired GARP+CD4+CD25+ Regulatory T Cells from Patients with Acute Coronary Syndrome by Upregulating LAP and GARP Expression on Activated T Lymphocytes
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Heme Oxygenase-1 Restores Impaired GARP+CD4+CD25+ Regulatory T Cells from Patients with Acute Coronary Syndrome by Upregulating LAP and GARP Expression on Activated T Lymphocytes

机译：血红素加氧酶-1通过上调活化T淋巴细胞的LAP和GARP表达来恢复急性冠脉综合征患者受损的GARP + CD4 + CD25 +调节性T细胞。

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Background: Accumulating evidence shows that the pathological autoreactive immune response is responsible for plaque rupture and the subsequent onset of acute coronary syndrome (ACS). Naturally occurring CD4+CD25+regulatory T cells (nTregs) are indispensable in suppressing the pathological autoreactive immune response and maintaining immune homeostasis. However, the number and the suppressive function of glycoprotein-A repetitions predominant (GARP) + CD4+ CD25+ activated nTregs were impaired in patients with ACS. Recent evidence suggests that heme oxygenase-1 (HO-1) can regulate the adaptive immune response by promoting the expression of Foxp3. We therefore hypothesized that HO-1 may enhance the function of GARP+ CD4+ CD25+Tregs in patients with ACS and thus regulate immune imbalance. Methods: T lymphocytes were isolated from healthy volunteers (control, n=30) and patients with stable angina (SA, n=40) or ACS (n=51). Half of these cells were treated with an HO-1 inducer (hemin) for 48 h, and the other half were incubated with complete RPMI-1640 medium. The frequencies of T-helper 1 (Th1), Th2, Th17 and latency-associated peptide (LAP) +CD4+ T cells and the expression of Foxp3 and GARP by CD4+CD25+T cells were then assessed by measuring flow cytometry after stimulation in vitro. The suppressive function of activated Tregs was measured by thymidine uptake. The levels of transforming growth factor-1 (TGF-β1) in the plasma were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of the genes encoding these proteins were analyzed by real-time polymerase chain reaction. Results: Patients with ACS exhibited an impaired number and suppressive function of GARP+ CD4+ CD25+Tregs and a mixed Th1/Th17-dominant T cell response when compared with the SA and control groups. The expression of LAP in T cells was also lower in patients with ACS compared to patients with SA and the control individuals. Treatment with an HO-1 inducer enhanced the biological activity of GARP+ CD4+ CD25+Tregs and resulted in increased expression of LAP and GARP by activated T cells. Conclusions: The reduced number and impaired suppressive function of GARP+ CD4+ CD25+Tregs result in excess effector T cell proliferation, leading to plaque instability and the onset of ACS. HO-1 can effectively restore impaired GARP+ CD4+ CD25+Tregs from patients with ACS by promoting LAP and GARP expression on activated T cells.
机译：背景：越来越多的证据表明，病理性自身反应性免疫反应是导致斑块破裂和随后发生急性冠状动脉综合征（ACS）的原因。天然存在的CD4 + CD25 + 调节性T细胞（nTregs）在抑制病理性自身反应性免疫应答和维持免疫稳态方面必不可少。然而，糖蛋白A重复优势（GARP） + CD4 + CD25 + 激活的nTregs的数量和抑制功能受损。 ACS。最近的证据表明，血红素加氧酶-1（HO-1）可以通过促进Foxp3的表达来调节适应性免疫反应。因此，我们假设HO-1可能增强ACS患者GARP + CD4 + CD25 + Treg的功能，从而调节免疫失衡。方法：从健康志愿者（对照组，n = 30）和稳定型心绞痛（SA，n = 40）或ACS（n = 51）患者中分离出T淋巴细胞。这些细胞中的一半用HO-1诱导剂（血红素）处理48小时，另一半则用完全RPMI-1640培养基孵育。 T辅助细胞1（Th1），Th2，Th17和潜伏期相关肽（LAP） + CD4 + T细胞的频率以及CD4对Foxp3和GARP的表达然后在体外刺激后通过测量流式细胞仪评估 + CD25 + T细胞。通过胸苷摄取来测量活化的Treg的抑制功能。使用酶联免疫吸附测定（ELISA）测量血浆中转化生长因子1（TGF-β1）的水平。通过实时聚合酶链反应分析编码这些蛋白质的基因的表达水平。结果：ACS患者的GARP + CD4 + CD25 + Tregs和混合的Th1 / Th17占主导的T的数目和抑制功能受损与SA和对照组比较时的细胞反应。与SA患者和对照组相比，ACS患者T细胞中LAP的表达也较低。 HO-1诱导剂处理增强了GARP + CD4 + CD25 + Treg的生物活性，并导致LAP和GARP的表达增加。活化的T细胞。结论：GARP + CD4 + CD25 + Treg的数量减少和抑制功能受损，导致效应子T细胞过度增殖，导致斑块不稳定。和ACS的发作。 HO-1可以通过促进活化T细胞上的LAP和GARP表达来有效恢复ACS患者受损的GARP + CD4 + CD25 + Treg。

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