AUTHOR=Wang Xinzhi , Sun Lixin , Zhang Luyong , Jiang Zhenzhou 

TITLE=Effect of Adoptive Transfer or Depletion of Regulatory T Cells on Triptolide-induced Liver Injury

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 7 - 2016

YEAR=2016

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2016.00099

DOI=10.3389/fphar.2016.00099

ISSN=1663-9812

ABSTRACT=Objective
The aim of this study is to clarify the role of regulatory T cell (Treg) in triptolide (TP)-induced hepatotoxicity. 
Methods
Female C57BL/6 mice received either adoptive transfer of Tregs or depletion of Tregs, then underwent TP administration and were sacrificed 24 hours after TP administration. Liver injury was determined according to ALT and AST levels in serum and histopathological change in liver tissue. Hepatic frequencies of Treg cells and the mRNA expression levles of transcription factor FoxP3 and RORγt, IL-10, SOCS and Notch/Notch ligand were investigated.
Results
During TP-induced liver injury, hepatic Treg and IL-10 decreased, while Th17 cell transcription factor RORγt, SOCS signaling and Notch signaling increased, accompanied with liver inflammation. Adoptive transfer of Tregs ameliorated the severity of TP-induced liver injury, accompanied with increased levels of hepatic Treg and IL-10. Adoptive transfer of Tregs remarkably inhibited the expression of RORγt, SOCS3, Notch1 and Notch3. On the contrary, depletion of Treg cells in TP-administered mice resulted in a notable increase of RORγt, SOCS1, SOCS3 and Notch3, while the Treg and IL-10 of liver decreased. Consistent with the exacerbation of liver injury, higher serum levels of ALT and AST were detected in Treg-depleted mice. 
Conclusions
These results showed that adoptive transfer or depletion of Tregs attenuated or aggravated TP-induced liver injury, suggesting that Tregs could play important roles in the progression of liver injury. SOCS proteins and Notch signaling affected Tregs, which may contribute to the pathogenesis of TP-induced hepatotoxicity.