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HRA002607
   HRA002607.xlsx
Title:
CD177+ cells produce neutrophil extracellular traps to promote biliary atresia
Release date:
2022-07-28
Description:
Immune dysregulation known to be critical in biliary atresia (BA), but the role of innate immune cells remains unclear. In a rotavirus-induced BA model in NOD/SCID mice, increased levels of Gr-1+ cells in the liver were observed. Single-cell RNA-sequencing analysis revealed that CD177+ cells were the main population of Gr-1+ cells and expressed elevated levels of both interferon-stimulated and neutrophil degranulation genes. CD177-/- BALB/c mice had a delayed disease onset and reduced morbidity and mortality. High numbers of mitochondria were detected in BA CD177+ cells with increased levels of ROS and neutrophil extracellular trap (NET), which induced the apoptosis of cholangiocytes in cocultures. In a pilot clinical study, the administration of a NET inhibitor to BA patients resulted in reduced CD177+ cell numbers and ROS levels, suggesting a potential beneficial effect. Our data indicate that CD177+ cells play an important role in the initiation of BA pathogenesis via NET formation.
Data Accessibility:   
Controlled access Request Data
BioProject:
PRJCA006035
Study type:
Disease Study
Disease name:
biliary atresia
Data Access Committee

For each controlled access study, there is a corresponding Data Access Committee(DAC) to determine the access permissions. Access to actual data files is not managed by NGDC.


DAC NO.:
HDAC000684
DAC name:
CD177+ cells and biliary atresia
Contact person:
ZHANG RUIZHONG
Email:
cowboy2006@163.com
Description:
Immune dysregulation known to be critical in biliary atresia (BA), but the role of innate immune cells remains unclear. In a rotavirus-induced BA model in NOD/SCID mice, increased levels of Gr-1+ cells in the liver were observed. Single-cell RNA-sequencing analysis revealed that CD177+ cells were the main population of Gr-1+ cells and expressed elevated levels of both interferon-stimulated and neutrophil degranulation genes. CD177-/- BALB/c mice had a delayed disease onset and reduced morbidity and mortality. High numbers of mitochondria were detected in BA CD177+ cells with increased levels of ROS and neutrophil extracellular trap (NET), which induced the apoptosis of cholangiocytes in cocultures. In a pilot clinical study, the administration of a NET inhibitor to BA patients resulted in reduced CD177+ cell numbers and ROS levels, suggesting a potential beneficial effect. Our data indicate that CD177+ cells play an important role in the initiation of BA pathogenesis via NET formation.
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Submitter:   ZHANG RUIZHONG / cowboy2006@163.com
Organization:   Guangzhou Women and Children's Medical Center
Submission date:   2021-08-04
Requests:   -