Department of Biomaterials Science and Technology, Technical Medical Centre, Faculty of Science and Technology, University of Twente, Enschede, Netherlands.
Department of Pediatric and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Front Immunol. 2020 Feb 25;11:329. doi: 10.3389/fimmu.2020.00329. eCollection 2020.
Biliary atresia (BA) is a devastating fibro-inflammatory disease characterized by the obstruction of extrahepatic and intrahepatic bile ducts in infants that can have fatal consequences, when not treated in a timely manner. It is the most common indication of pediatric liver transplantation worldwide and the development of new therapies, to alleviate the need of surgical intervention, has been hindered due to its complexity and lack of understanding of the disease pathogenesis. For that reason, significant efforts have been made toward the development of experimental models and strategies to understand the etiology and disease mechanisms and to identify novel therapeutic targets. The only characterized model of BA, using a Rhesus Rotavirus Type A infection of newborn BALB/c mice, has enabled the identification of key cellular and molecular targets involved in epithelial injury and duct obstruction. However, the establishment of an unleashed chronic inflammation followed by a progressive pathological wound healing process remains poorly understood. Like T cells, macrophages can adopt different functional programs [pro-inflammatory (M1) and resolutive (M2) macrophages] and influence the surrounding cytokine environment and the cell response to injury. In this review, we provide an overview of the immunopathogenesis of BA, discuss the implication of innate immunity in the disease pathogenesis and highlight their suitability as therapeutic targets.
先天性胆道闭锁（BA）是一种破坏性的纤维炎症性疾病，其特征是婴儿的肝外和肝内胆管阻塞，如果不及时治疗，可能会导致致命后果。它是全球小儿肝移植最常见的适应证，由于其复杂性和对疾病发病机制的缺乏了解，新疗法的开发一直受到阻碍，以减轻对手术干预的需求。因此，人们做出了巨大的努力来开发实验模型和策略，以了解病因和疾病机制，并确定新的治疗靶点。唯一使用恒河猴轮状病毒 A 型感染新生 BALB/c 小鼠的 BA 特征模型，使我们能够确定参与上皮损伤和胆管阻塞的关键细胞和分子靶点。然而，尚未完全了解未受抑制的慢性炎症后进行的进行性病理性伤口愈合过程。与 T 细胞一样，巨噬细胞可以采用不同的功能程序（促炎（M1）和修复（M2）巨噬细胞），并影响周围的细胞因子环境和细胞对损伤的反应。在这篇综述中，我们概述了 BA 的免疫发病机制，讨论了固有免疫在疾病发病机制中的作用，并强调了它们作为治疗靶点的适用性。
