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首页> 外文期刊>Frontiers in Pediatrics >CD4 + T Cell Subset Profiling in Biliary Atresia Reveals ICOS ? Regulatory T Cells as a Favorable Prognostic Factor
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CD4 + T Cell Subset Profiling in Biliary Atresia Reveals ICOS ? Regulatory T Cells as a Favorable Prognostic Factor

机译：胆道Atresia中的CD4 + T细胞剖面概览揭示了ICOS？ 调节性T细胞作为良好的预后因子

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Biliary atresia (BA) is a destructive pediatric liver disease and CD4 + T cell activation is demonstrated to play an important role in BA. However, a comprehensive scenario regarding the involvement of CD4 + T cell subsets to the development of BA remains unclear. Here, we aim to explore the infiltration of CD4 + T cell subsets and their clinical significance in BA. In the present study, thirty BA liver samples were collected during surgery and were divided into good (BA1, n = 16) and poor prognosis (BA2, n = 14), with samples from choledochal cyst patients ( n = 8) as control. By using multiplex immunohistochemistry, we evaluated the infiltration level of CD4 + T cell subsets in the portal areas. RT-qPCR and flow cytometry were further applied to explore detailed features of Treg subsets. We revealed that hepatic infiltrating Th1, Th2, Th17, and ICOS + Treg cells were significantly increased in BA patients compared to controls and were negatively associated with prognosis, while high infiltrating ICOS ? Tregs showed a favorable outcome. Phenotypic analysis indicated that, in contrast to ICOS + Tregs, ICOS ? Tregs were mainly CD45RA hi CD45RO low , and preferentially expressed more CD73. Besides, RT-qPCR revealed elevated expression of CD25, CD73, TGF- β, and BCL-2 genes in ICOS ? Tregs. Finally, functional assay confirmed that ICOS ? Tregs had a higher suppressive capacity to cytokine secretion and were more resistant to apoptosis in vitro . Collectively, we demonstrate that a mixed immune response is involved in BA pathogenesis, and the globally enhanced effector CD4 + T cell response is associated with unfavorable prognosis, highly suppressive ICOS ? Tregs is a protective factor and may serve an important reference to predict prognosis.
机译：胆道休息（BA）是一种破坏性的儿科肝病，并证明CD4 + T细胞活化在BA中发挥着重要作用。然而，关于CD4 + T细胞亚群与BA发展的累及的全面情景仍不清楚。在这里，我们的目的是探讨CD4 + T细胞亚群的渗透及其在BA中的临床意义。在本研究中，在手术期间收集了30个BA肝脏样品，并分为良好（BA1，N = 16）和预后差（BA2，N = 14），其中来自Choledochal囊肿患者的样品（n = 8）作为对照。通过使用多重免疫组织化学，我们在门户区域中评估了CD4 + T小区子集的渗透水平。进一步应用RT-QPCR和流式细胞仪以探索Treg子集的详细特征。我们透露，与对照组相比，BA患者肝脏浸润Th1，Th2，Th17和ICOS + Treg细胞显着增加，并且与预后与预后负相关，而高渗透ICOS？ Tregs表现出有利的结果。表型分析表明，与ICOS + Tregs相比，ICOS相反？ Tregs主要是CD45ra HI CD45RO低，优先表达了更多CD73。此外，RT-QPCR揭示了ICOS中CD25，CD73，TGF-β和BCL-2基因的升高表达吗？ tregs。最后，功能试验证实了ICOS？ Tregs对细胞因子分泌具有更高的抑制能力，并且在体外更耐细胞凋亡。总的来说，我们证明了混合免疫应答参与了BA发病机制，而全球增强的效应CD4 + T细胞反应与不利预后，高度抑制的ICO有关？ Tregs是一种保护因素，可以用于预测预后的重要参考。

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