Adoptive transfer of hepatic stellate cells ameliorates liver ischemia reperfusion injury through enriching regulatory T cells.
Our previous study indicated that adoptive transferred regulatory T cells (Tregs) attenuated liver ischemia reperfusion injury (IRI). Recent studies demonstrated that hepatic stellate cells (HSCs) were producers of induced Tregs (iTregs) via retinoic acid. This study aimed to investigate the role of adoptive transferred HSCs in liver IRI. Mice were treated with gradient doses of HSCs before surgery at 24h or 72h. The levels of serum aminotransferases and hepatic cytokines were evaluated after reperfusion. Meanwhile, hepatic Tregs and their subsets were analyzed by flow cytometry. We found that adoptive transferred HSCs attenuated liver IRI. Administration of HSCs expanded the number of hepatic iTregs and natural Tregs (nTregs) after reperfusion. In addition, we found that the increased Tregs were almost Helios-Tregs before surgery. These Helios-Tregs were considered as iTregs and protected liver from IRI partially. Furthermore, adoptive transferred HSCs stabilized nTregs and prevented nTregs from reducing after reperfusion. These nTregs also attenuated liver IRI partially. Depletion of Tregs abolished the protective effect of HSCs. Thus, we conclude that adoptive transferred HSCs ameliorate liver IRI in Tregs-dependent manner.
Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
Min
M
Feng
Radiology Department, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Living Donor Liver Transplantation of Ministry of Public Health, Nanjing 210029, China.
Quanrongzi
Q
Wang
Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
Hao
H
Wang
Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
Meng
M
Wang
Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China. Electronic address: Guan-wx@163.com.
Wenxian
W
Guan
Key Laboratory of Living Donor Liver Transplantation of Ministry of Public Health, Nanjing 210029, China.
Ling
L
Lu
D019264:Adoptive Transfer; D000818:Animals; D055166:Hepatic Stellate Cells; D008107:Liver Diseases / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
Hepatic stellate cells; Ischemia reperfusion injury; Liver; Regulatory T cells