Restoration of intrahepatic regulatory T cells through MMP-9/13-dependent activation of TGF-β is critical for immune homeostasis following acute liver injury

Ling Lu, Min Feng, Jia Gu, Zanxian Xia, Hongjun Zhang, Sujun Zheng, Zhongping Duan, Richard Hu, Julie Wang, Wei Shi, Cheng Ji, Yi Shen, Guihua Chen, Song Guo Zheng, Yuan Ping Han

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

During the acute liver injury, immune responses are provoked into eliciting inflammation in the acute phase. In the healing phase, the inflammation is terminated for wound healing and restoration of immune homeostasis. In this study, we sought to address how regulatory T cells (Tregs) are involved in the progression of liver injury and repair. In the acute phase, intrahepatic Tregs (CD4+FoxP3+Helios+) diminished promptly through apoptosis, which was followed by inflammation and tissue injury. In the healing phase, a new subset of Tregs (CD4+Foxp3+Helios -) was generated in correlation with the matrix metalloproteinase (MMP) cascade and transforming growth factor-beta (TGF-β) activation that were manifested mainly by hepatic stellate cells. Moreover, the induction of induced Tregs and wound healing were both impaired in mice lacking TGF-β signaling or MMPs. The depletion of induced Tregs also impeded wound healing for tissue repair. Together, this study demonstrates the mechanism that the loss of nTregs through apoptosis in the acute phase may facilitate inflammation, while regenerated Tregs through MMP9/13-dependent activation of TGF-β in the healing phase are critical to terminate inflammation and allow for wound healing.

Original languageEnglish (US)
Pages (from-to)369-379
Number of pages11
JournalJournal of Molecular Cell Biology
Volume5
Issue number6
DOIs
StatePublished - Dec 2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cell Biology

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