Introduction T helper (Th)17 cells, a newly identified subset of Th cells, are major mediators of inflammation-associated disease and have a reciprocal developmental relationship with the immunosuppressive T regulatory (Treg) cells, which actively restrain the inflammatory response. The present work was designed to study the balance between Th17 cells and Treg cells in patients with chronic hepatitis C (CHC) in relation to disease activity and severity of hepatic fibrosis.
Methods Twenty patients with treatment-naive CHC and 20 healthy subjects were included in the study. The Th cells, Th17 cells and Treg cell subsets in fresh whole blood samples were identified as CD3+CD4+, CD4+IL17A+ and CD4+CD25+FoxP3+ cells respectively using flow cytometry and expressed as percentages of total lymphocytic count. Serum IL17 levels were measured using solid phase sandwich enzyme linked immunosorbant assay kit. Liver biopsies from patients with CHC were examined to assess histological activity grade and fibrosis stage according to METAVIR scoring system. Liver-infiltrating CD4+ (Th cells), IL17A+ cells (Th17 cells) and FoxP3+ cells (Treg cells) were detected by immunohistochemical staining and their proportions were determined as ratios of infiltrating CD4+ Th cells.
Results Patients with CHC showed significant increases in the percentage of Th17 cells, Th17 cells/FoxP3+Treg cells ratio in peripheral blood and serum IL17 levels and a significant decrease in the percentage of circulating FoxP3+Treg cells compared with healthy subjects (p<0.01). The percentages of peripheral blood CD4+ Th cells were not statistically different between the two groups (p=0.284). The proportions of liver-infiltrating IL17A+ cells and FoxP3+ cells of the total intrahepatic CD4+ cell population were inversely correlated and showed positive correlations with the percentages of circulating Th17 cells and FoxP3+ Treg cells respectively in patients with CHC (p<0.05). The METAVIR necroinflammation grade and fibrosis stage [but not serum HCV RNA levels] were directly correlated with the proportion of intrahepatic IL17A+ cells and IL17A+ cells/FoxP3+ cells ratio and serum IL17 levels and were inversely correlated with the proportion of liver-infiltrating FoxP3+ cells (p<0.05).
Conclusion In patients with CHC, the CD4+ Th cell phenotype is skewed towards the IL17 producing-Th phenotype. The imbalance between Th17 and Foxp3+ Treg cells plays an important role in disease progression and hepatic fibrosis in CHC.
Competing interests None declared.
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