Intrahepatic Th17/Treg interplay related to fibrosis in Chronic Hepatitis C

RÍOS D; FRÍAS S.; DE MATTEO E; MULLEN E; CASCIATO P; GALDAME O; AMEIGEIRAS B; BRODERSEN C; VALVA P; MARIA VICTORIA PRECIADO

Boston

Congreso; Meeting of the American Association for the Study of the Liver (AASLD); 2016

American Association for the Study of Liver Diseases

Regulatory CD4+ T cells (Tregs) are considered to affect HCV infection outcome, but little is known about the effect of Th17/Treg interplay and other T cell subpopulations. Our aim was to explore liver microenvironment with its peripheral blood (PB) reflex to elucidate their role in Chronic Hepatitis C (CHC) pathogenesis.Liver biopsies and concomitant PB samples from 27 adult CHC patients treatment naïve [median(range)=52yr (32-72)] were analysed. The frequency (lymphocyte+/total lymphocyte) of T cytotoxic (Tc) and T helper (Th) cells as well as Th subpopulations (Treg, Th17, Th1) were determined in formalin-fixed biopsies and PB samples by immunohistochemistry or flow cytometry, respectively. PB samples of uninfected donors were also included. IL10, IL17, TGFβ, IL6, IFNγ and TNFα mRNA expression levels were quantified in fresh liver biopsies by RT-qPCR. The results were integrated and evaluated in the context of liver damage.No difference in lymphocyte population frequency in PB were depicted between patients and donors; they were not associated with liver damage either. There were no correlation between compartments (PB vs liver) for each population.Intrahepatic lymphocytes in portal/periportal infiltrates showed Th predominance (Th>Tc> Treg>Th1>Th17). Treg was the most frequent Th subpopulation [0.15 (0.02-0.29)] and displayed association with lower fibrosis stages (p=0.02); in turn Th17 was the less frequent [0.07 (0.01-0.26)]. The Th17/Treg correlated with higher fibrosis stages (p=0.03, r=0.45). In relation to cytokine liver microenvironment, IL10 higher levels were associated with lower fibrosis stages (p=0.03) but did not correlate with Treg frequency. IL17 was detected in a very low level only in few samples. The ratios TGFβ/IL6 and Th17/Treg positively correlated each other (p=0.005, r=0.6). IFNγ, TNFα and TGFβ showed positive correlation each other (all p