调节性 T 细胞抑制鼠先天性胆道闭锁中 Th1 细胞介导的胆管损伤。
Regulatory T cells inhibit Th1 cell-mediated bile duct injury in murine biliary atresia.
机构信息
University of Colorado, Denver, United States.
出版信息
J Hepatol. 2013 Oct;59(4):790-6. doi: 10.1016/j.jhep.2013.05.010. Epub 2013 May 14.
BACKGROUND & AIMS: Biliary atresia (BA) is a pediatric inflammatory disease of the biliary system which leads to cirrhosis and the need for liver transplantation. One theory regarding etiology is that bile duct injury is due to virus-induced autoreactive T cell-mediated inflammation. Regulatory T cell (Treg) abnormalities in BA could result in unchecked bystander inflammation and autoimmunity targeting bile ducts. The aim of this study was to determine if Tregs are dysfunctional in the rotavirus-induced mouse model of BA (murine BA).
METHODS
Murine BA resulted from infection of BALB/c neonates with Rhesus rotavirus (RRV).
RESULTS
Liver Tregs from BA mice were decreased in number, activation marker expression, and suppressive function. Adoptive transfer studies revealed that RRV-infected mice that received Tregs had significantly increased survival (84%) compared to controls (12.5%). In addition, ablation of Tregs in older mice, followed by RRV infection, resulted in increased bile duct injury.
CONCLUSIONS
These studies demonstrate that dysregulation of Tregs is present in murine BA and that diminished Treg function may be implicated in the pathogenesis of human BA.
背景与目的
胆道闭锁（BA）是一种儿童期胆道系统的炎症性疾病，可导致肝硬化并需要进行肝移植。一种关于病因的理论认为，胆管损伤是由病毒诱导的自身反应性 T 细胞介导的炎症引起的。BA 中的调节性 T 细胞（Treg）异常可能导致不受控制的旁观者炎症和针对胆管的自身免疫。本研究旨在确定 Treg 是否在轮状病毒诱导的 BA 小鼠模型（鼠 BA）中功能失调。
方法
BA 由 BALB/c 新生儿感染恒河猴轮状病毒（RRV）引起。
结果
BA 小鼠的肝脏 Treg 数量减少，激活标志物表达和抑制功能降低。过继转移研究表明，接受 Treg 的 RRV 感染小鼠的存活率（84%）明显高于对照组（12.5%）。此外，在老年小鼠中清除 Treg 后再感染 RRV，导致胆管损伤增加。
结论
这些研究表明，鼠 BA 中存在 Treg 失调，Treg 功能降低可能与人类 BA 的发病机制有关。
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