Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC) and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Division of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
JCI Insight. 2020 Jun 4;5(11):135751. doi: 10.1172/jci.insight.135751.
Extramedullary hematopoietic cells are present in the liver of normal neonates in the first few days of life and persist in infants with biliary atresia. Based on a previous report that liver genes are enriched by erythroid pathways, we examined the liver gene expression pattern at diagnosis and found the top 5 enriched pathways are related to erythrocyte pathobiology in children who survived with the native liver beyond 2 years of age. Using immunostaining, anti-CD71 antibodies identified CD71+ erythroid cells among extramedullary hematopoietic cells in the livers at the time of diagnosis. In mechanistic experiments, the preemptive antibody depletion of hepatic CD71+ erythroid cells in neonatal mice rendered them resistant to rhesus rotavirus-induced (RRV-induced) biliary atresia. The depletion of CD71+ erythroid cells increased the number of effector lymphocytes and delayed the RRV infection of livers and extrahepatic bile ducts. In coculture experiments, CD71+ erythroid cells suppressed the activation of hepatic mononuclear cells. These data uncover an immunoregulatory role for CD71+ erythroid cells in the neonatal liver.
骨髓外造血细胞存在于正常新生儿肝脏中，在胆道闭锁婴儿的肝脏中持续存在。基于之前的报告，肝脏基因被红细胞途径富集，我们在诊断时检查了肝脏基因表达模式，发现前 5 个富集途径与在 2 岁以上保留自身肝脏的儿童的红细胞病理生物学有关。使用免疫染色，抗 CD71 抗体在诊断时鉴定了骨髓外造血细胞中的 CD71+红细胞。在机制实验中，新生小鼠肝脏中 CD71+红细胞的抢先抗体耗竭使它们能够抵抗恒河猴轮状病毒诱导的（RRV 诱导的）胆道闭锁。CD71+红细胞的耗竭增加了效应淋巴细胞的数量，并延迟了 RRV 对肝脏和肝外胆管的感染。在共培养实验中，CD71+红细胞抑制了肝单核细胞的激活。这些数据揭示了 CD71+红细胞在新生儿肝脏中的免疫调节作用。
