Foxp3Expression in Liver Correlates with the Degree but Not the Cause of Inflammation

Abstract

Patients with chronic viral hepatitis display increased expression ofFoxp3in liver, suggesting that Tregs expansion contributes to persistent infection. The purpose of this study was to elucidate whether the expression ofFoxp3relates not to the viral infection but to the resulting liver inflammation. Liver biopsies obtained from 69 individuals (26 chronic HBV hepatitis, 14 chronic HCV hepatitis, 11 nonalcoholic fatty liver disease, 8 autoimmune diseases, 2 methotrexate-related toxicity, and 8 controls) were examined, by qRT-PCR, for the mRNA expression ofFoxp3,IL-10,TGF-β1,Fas, FasL, TRAIL, caspase-3, TNF-α, IFN-γ,andIL-1β. Significant increase ofFoxp3was observed in all disease groups compared to controls, which was positively correlated with the intensity of inflammation. The expression of the apoptosis mediatorsFas, FasL, andTRAIL, but not ofIL-10andTGF-β1, was also significantly elevated. Our findings indicate that, independently of the initial inducer, liver inflammation is correlated with elevated expression of apoptosis mediators and is followed by local Treg accumulation. Further research towards the elucidation of the underlying casual relationships is required, in order to clarify whether our results signify the existence of a uniform Treg-mediated regulatory mechanism of apoptosis-induced inflammation.