Chronic hepatitis C liver microenvironment: role of the Th17/Treg interplay related to fibrogenesis

The role of the different lymphocyte populations in liver microenvironment of chronic hepatitis C (CHC) patients is still matter of debate. Since Th17 and Treg have opposite functions, their balance could affect disease progression. The aim was to explore liver microenvironment and its peripheral blood counterpart in adult CHC patients. CD4(+) lymphocytes were predominant in the liver, with high Foxp3(+) but low IL-17A(+) frequency. IL-17A(+) lymphocytes and IL-17A(+)/Foxp3(+) ratio displayed association with advanced fibrosis (p = 0.0130; p = 0.0236, respectively), while Foxp3(+) lymphocytes and IL-10 expression level inversely correlated with fibrosis severity (p = 0.0381, p = 0.0398, respectively). TGF-beta/IL-6 ratio correlated with IL-17A(+)/Foxp3(+) ratio (p = 0.0036, r = 0.5944) and with IL-17A(+) lymphocytes (p = 0.0093; r = 0.5203). TNF-alpha and TGF-beta were associated with hepatitis severity (p = 0.0409, p = 0.0321). Peripheral blood lymphocyte frequency was not associated with liver damage. There are functionally different immune cell populations actively involved in liver damage, but the liver cytokine milieu actually drives the pathogenesis. The intrahepatic Foxp3(+) lymphocytes predominance beside the low IL-17A(+) lymphocytes frequency, delineate a skewed IL-17A(+)/Foxp3(+) balance towards Foxp3(+) lymphocytes. However, the IL-17A(+) lymphocytes association with advanced fibrosis denotes their role in the pathogenesis. Therefore, the interplay between Th17 and Treg conditions liver fibrogenesis.