期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 12, 期 1, 页码 189-196出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2011.11.010
关键词
Ischemia reperfusion injury; Regulatory T cells; Kupffer cells; TGF-beta
资金
- International Collaborationl Foundation of Jiangsu Province [BZ2011041, BK2009439, ZX05 200904]
- National Nature Science Foundation of China [81100270, 81070380, 81170415]
In the presence of TGF-beta, CD4+CD62L+T cells can be induced to CD4+CD25+FoxP3 + regulatory T cells (iTregs). In our previous work, we have shown that adoptive transfer of iTregs promoted liver recovery from ischemia reperfusion injury (IRI). In this study, we examined the molecular mechanism underlying the liver IRI attenuation by iTregs in a mouse partial hepatic IRI model. We found that the population of hepatic Tregs decreased significantly at 24 h after reperfusion. Adoptive transfer of iTregs before IRI markedly increased the numbers of hepatic Tregs and attenuated liver IRI as indicated by reduced serum aminotransferases and proinflammatory cytokines, such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha). Ex vivo study indicated that iTregs suppressed IL-1 beta and TNF-alpha expression, promoted transcription of interleukin-10 (IL-10), and elevated phosphorylation of SMAD3 in Kupffer cells (KCs). Furthermore, inhibition of TGF-beta signaling by anti-TGF-beta abolished the effects on KCs. Treatment with TGF-beta, suppressed matrix metalloprotease (MMP9) production in KCs and protected liver from IRI. In conclusion, our results suggest that iTregs play a critical role in hepatic IRI by regulating pro-inflammatory and anti-inflammatory function of KCs through TGF-beta. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.
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