Dendritic Cells Regulate Treg-Th17 Axis in Obstructive Phase of Bile Duct Injury in Murine Biliary Atresia

PloS One
Yong-jun LiuXi Zhang

Abstract

Several cell types are considered to be effector cells in bile duct injury in rhesus rotavirus (RRV)-induced experimental biliary atresia (BA). Here, we identified an increased T helper 17 (Th17) cell population in a BA mode. By depleting the Th17 cells, the BA symptoms (onset of jaundice, acholic stools and retarded growth) were attenuated and the survival rate was improved. Furthermore, we found that in mice with BA, the percentage of CD4+CD25highFoxp3+ T regulatory (Treg) cells decreased along with the increased percentage of Th17 cells. However, the absolute numbers of Treg and Th17 cells were both increased in liver of RRV-injected mice compared to saline-injected mice. The proportion of Th17 cells at 7 days post-infection was decreased if Treg cells isolated from normal adult mice, but not Treg cells from the livers of mice with BA, were intraperitoneally transferred on day 5 of life. In vitro experiments also showed that Treg cells from mice with BA had a diminished suppressive effect on Th17 cell generation. To determine the mechanisms, we investigated the production of cytokines in the liver. The level of IL-6, which has been shown to be abundantly secreted by activated dendritic cells (DCs), was remarkably elevated. I...Continue Reading

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Citations

May 6, 2016·Frontiers in Pharmacology·Xinzhi WangZhenzhou Jiang
Jan 13, 2016·Journal of Pediatric Gastroenterology and Nutrition·Carsten EngelmannHermann Kreyenberg
Sep 24, 2016·American Journal of Physiology. Gastrointestinal and Liver Physiology·Kang LiShao-Tao Tang

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Methods Mentioned

BETA
FACS
ELISA
flow cytometry
PCR
PMA

Software Mentioned

CellSens
FlowJo

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