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CD4(+)T Cell Subset Profiling in Biliary Atresia Reveals ICOS- Regulatory T Cells as a Favorable Prognostic Factor 期刊论文

编号：

6399285b-81e2-422a-a43e-70fdc9535c2e
作者：

Zhang, Shuhao#^[1]Goswami, Shyamal#^[2]Ma, Jiaqiang#^[2]Meng, Lu^[2];Wang, Youping^[2];Zhu, Fangming^[2];Zhang, Dandan^[3];Zheng, Shan(郑珊)^[1]Dong, Rui(董瑞)^[1]Xiao, Xianmin^[1];Zhang, Xiaoming*^[2]Chen, Gong(陈功)*^[1]
语种：

英文
期刊：

FRONTIERS IN PEDIATRICS ISSN：2296-2360 2019 年 7 卷 ; JUL 9
收录：
关键词：

biliary atresia immune dysfunction CD4(+)T cell subset inducible co-stimulator prognosis
摘要：

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-beta, 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.
推荐引用方式
GB/T 7714：

Zhang Shuhao,Goswami Shyamal,Ma Jiaqiang, et al. CD4(+)T Cell Subset Profiling in Biliary Atresia Reveals ICOS- Regulatory T Cells as a Favorable Prognostic Factor [J].FRONTIERS IN PEDIATRICS,2019,7.
APA：

Zhang Shuhao,Goswami Shyamal,Ma Jiaqiang,Meng Lu,&Chen Gong.(2019).CD4(+)T Cell Subset Profiling in Biliary Atresia Reveals ICOS- Regulatory T Cells as a Favorable Prognostic Factor .FRONTIERS IN PEDIATRICS,7.
MLA：

Zhang Shuhao, et al. "CD4(+)T Cell Subset Profiling in Biliary Atresia Reveals ICOS- Regulatory T Cells as a Favorable Prognostic Factor" .FRONTIERS IN PEDIATRICS 7(2019).
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