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

Abstract

Patients with chronic viral hepatitis display increased expression of Foxp3 in liver, suggesting that Tregs expansion contributes to persistent infection. The purpose of this study was to elucidate whether the expression of Foxp3 relates 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 of Foxp3, IL-10, TGF-β1, Fas, FasL, TRAIL, caspase-3, TNF-α, IFN-γ, and IL-1β. Significant increase of Foxp3 was observed in all disease groups compared to controls, which was positively correlated with the intensity of inflammation. The expression of the apoptosis mediators Fas, FasL, and TRAIL, but not of IL-10 and TGF-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.

Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection

“…This observation is also in accordance with previous reports [24,[50][51][52]. Moreover, although CD8 + /Foxp3 + cells have been described in CHC biopsies [31,53],they were under-represented in our studied series, as in other reports [51,52].…”

“…Accumulating evidence indicates that patients with chronic viral hepatitis display an increased number of Treg cells in peripheral blood or liver; however, the increment of Treg cells in CHC and their role in liver damage development is still a matter of debate [21][22][23][24][25][26].…”

Circulating Lysophosphatidylcholines Are Markers of a Metabolically Benign Nonalcoholic Fatty Liver

“…T regs secrete anti-inflammatory signals, inhibit macrophage migration, and induce noninflammatory M2-like macrophage differentiation (35). In addition, defects in T reg function are considered to play a role not only in autoimmune diseases, such as autoimmune hepatitis (36), but also in other causes of hepatic inflammation (37,38). In agreement with an anti-inflammatory property of lyso-PCs, we detected strong negative relationships of total lyso-PCs and lyso-PC C16:0 with hs-CRP levels in our subjects with NAFL.…”

Future Perspective: Immunomodulatory Therapy for Autoimmune Hepatitis

“…Instead, peripheral and intrahepatic Treg frequency correlated with disease activity. This is further supported by a report which showed that Treg frequency is generally elevated in inflamed livers irrespective of its cause [32]. If there is not a global defect of Treg numbers in AIH, the question rises why the attracted Treg are not able to suppress hepatic inflammation?…”