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Regulation of bile duct epithelial injury by hepatic CD71+ erythroid cells

Li Yang1,2, Pranavkumar Shivakumar1, Jeremy Kinder3

  • 1Division 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.

JCI Insight
|May 15, 2020
PubMed

Insights

CD71+ erythroid cells in neonatal livers regulate immunity. Depleting these cells protected mice from biliary atresia, revealing their role in immune suppression and disease resistance.

Area of Science:

  • Hepatology
  • Immunology
  • Neonatal Research

Background:

  • Extramedullary hematopoietic cells, including erythroid cells, are found in neonatal livers.
  • These cells persist in infants with biliary atresia and are linked to erythrocyte pathways in the liver.

Purpose of the Study:

  • To investigate the role of CD71+ erythroid cells in neonatal liver immunity and biliary atresia.
  • To determine if these cells possess immunoregulatory functions.

Main Methods:

  • Analysis of liver gene expression patterns in children with biliary atresia.
  • Immunostaining using anti-CD71 antibodies to identify erythroid cells.
  • Antibody-mediated depletion of hepatic CD71+ erythroid cells in neonatal mice.
  • Rhesus rotavirus (RRV) challenge model for biliary atresia.
  • Coculture experiments with hepatic mononuclear cells.

Main Results:

  • Top 5 enriched liver gene pathways in surviving children related to erythrocyte pathobiology.
  • CD71+ erythroid cells identified in neonatal livers at diagnosis.
  • Depletion of CD71+ erythroid cells conferred resistance to RRV-induced biliary atresia in mice.
  • CD71+ erythroid cell depletion increased effector lymphocytes and delayed viral spread.
  • CD71+ erythroid cells suppressed hepatic mononuclear cell activation in vitro.

Conclusions:

  • CD71+ erythroid cells play a significant immunoregulatory role in the neonatal liver.
  • These cells contribute to susceptibility to biliary atresia by suppressing immune responses.

Keywords:
Cellular immune responseHepatitisHepatologyMouse models

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