Fibrosis is the result of the abnormal accumulation of the extracellular matrix 
and ineffective clearance of fibroplasia. CD4(+)CD25(+)Foxp3(+) regulatory T 
cells (Tregs) are immunosuppressive lymphocytes that are highly expressed in the 
fibrotic tissues and peripheral blood of patients with cirrhosis or 
hepatocellular carcinoma. The role of Tregs in the progression of liver fibrosis 
is not well understood. Our experiments reveal that abundant of Tregs was 
scattered around sites of fibroplasia. Conversely, the depletion of Tregs 
promoted the resolution of liver fibrosis. As a consequence of Tregs depletion, 
the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of 
metalloproteinases (TIMPs) was altered; mmp9 and timp1 were reduced, whereas 
mmp2 and mmp14 were enhanced. The mmp9/timp1, mmp13/timp1, and mmp14/timp2 
ratios were significantly increased in association with fibrosis resolution. 
Kupffer cells (KCs) are the main source of MMP. We observed that when KCs were 
cocultured with Tregs, the Tregs were able to inhibit MMP expression of KCs even 
at a low ratio; and anti-transforming growth factor-β (TGF-β) significantly 
reversed the inhibition of Tregs on MMP. Meanwhile, we also found that after 
Tregs depletion, TGF-β levels decreased in the mice liver, unlike in fibrosis. 
Furthermore, double depletion of both KCs and Tregs did not cause fiber 
resolution in mice. Thus, our results demonstrate that the persistence of liver 
cirrhosis is maintained by increased Tregs in the sites of fibroplasia and the 
subsequent regulation of the MMP/TIMP balance and that the suppression of 
KC-mediated MMP expression contributed to the regulatory process.