In vitro induced CD4(+)CD25(+)Foxp3(+) Tregs attenuate hepatic ischemia-reperfusion injury.
Reperfusion injury causes liver dysfunction after warm or cold ischemia. Emerging data suggest a role of T cells as mediators in this ischemia/reperfusion (I/R) injury. In the T cells, a part of CD4(+)CD25(+)FoxP3(+) T regulatory cells (Tregs) were reported to facilitate recovery from I/R injury. These Tregs can be induced by TGF-beta in vitro. Interestingly, rapamycin was reported to selectively expand these Tregs in vitro. In the present study, addition of rapamycin to cultures containing TGF-beta further increased the frequency and absolute number of functional CD4(+) Tregs. Using a partial (70%) hepatic warm ischemia model, we investigated the effects of liver function recovery under the treatment of Tregs induced by rapamycin and TGF-beta. The treatment of Tregs significantly reduced serum alanine aminotransferase and aspartate aminotransferase compared to I/R control animals at 24 h after reperfusion (P<0.05). They also significantly attenuated the up-regulation of IFN-gamma and IL-17 compared to the I/R control animals (P<0.05). In conclusion, Tregs ameliorate the biochemical of hepatic I/R injury by preventing proinflammatory cytokines following a warm I/R insult. These data may pave the way to use Tregs as cell therapy to prevent hepatic I/R injury.
Lu
Ling
L
Key Laboratory of Living Donor Liver Transplantation of Ministry of Public Health, Nanjing, China.
Li
Guoqiang
G
Rao
Jianhua
J
Pu
Liyong
L
Yu
Yue
Y
Wang
Xuehao
X
Zhang
Feng
F
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit; D008099:Liver / Q000098:blood supply / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D020123:Sirolimus / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020123:Sirolimus