INVESTIGADORES
DE MATTEO Elena NoemÍ
congresos y reuniones científicas
Título:
Liver Th17/ Treg interplay related to pathogenesis of both chronic HBV and HCV infection
Autor/es:
GIADANS C*, RIOS D*, FRIAS S, HADDAD L , DE MATTEO E, MULLEN E, CASCIATO P, AMEIGEIRAS B, BRODERSEN C, GALDAME O, FLICHMAN D, VALVA P, PRECIADO MV
Lugar:
VIENA
Reunión:
Congreso; European Congress of Clinical Microbiology and Infectious Diseases (ECCMID); 2017
Institución organizadora:
ESCMID
Resumen:
Background: In viral chronic hepatitis, the immune system is involved in liver damage, but the role of each immune cell population is still unknown. It was suggested that T helper 17 (Th17) and regulatory T cells (Treg) balance is critical in the pathogenesis; however, its regulation was poorly understood. The study aim was to examine the role of Th17 and Tregs in chronic disease of both Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection. Material/methods: Th17/Treg interplay was explored in the portal/periportal infiltrate [IL17+ cells (Th17) and Foxp3+ cells (Treg)] by immunohistochemistry in formalin-fixed paraffin-embedded biopsies collected from untreated adult patients with chronic viral hepatitis (n=43; HBV=19, HCV=24). Immunostained/total lymphocytes were counted in all portal tracts (400). Inflammatory activity and fibrosis were assessed and recorded using the modified Knodell scoring system (Histological Activity Index, HAI) and METAVIR. The results were evaluated in the context of liver damage. Results: Both studied populations were observed in portal/periportal infiltrates, with predominance of Foxp3+ cells. There was no significant difference in the frequency of either Foxp3+ or IL17+ population between HBV and HCV cases [HBV: 0.11 (0-0.25), 0.05 (0-0.19); HCV: 0.16 (0.02-0.29), 0.07 (0.01-0.26), respectively]. Moreover, no differences were observed either in the IL17+/Foxp3+ cell ratio [HBV: 0.52 (0-5.57); HCV: 0.45 (0.04-5.02)] or in total lymphocyte count [HBV: 34.43 (7.5-50.47); HCV: 32.04 (12.84-70.9)] between both studied groups. Concerning liver damage, both groups displayed similar histopathological features (HBV: 42% significant fibrosis, 55% Moderate/severe HAI; HCV: 62% significant fibrosis, 75% Moderate/severe HAI; p fibrosis=0.34, Fisher test, p HAI=0.38, Chi-square test). IL17+ cells depicted positive association with fibrosis severity in both HBV (p=0.004, Student-test) and HCV (p=0.013, Mann-Whitney test) cases; while no association with hepatitis was observed in any case. Although its high frequency, Foxp3+ cells showed association with neither hepatitis nor fibrosis. Finally, the IL17+/Foxp3+ cell ratio was associated with advanced fibrosis (p=0.024, Mann-Whitney test) only in HCV cases. Conclusion: The pathogenesis of viral hepatitis is a complex process involving several immune cell populations. Since Tregs and Th17 cells have antagonist functions, dynamic changes in their frequency as well as the Th17/Treg ratio may be associated with liver pathogenesis. It is well known that Treg cells participate in a delicate balance between protective immunity and injury mediated immunity, although in our series Foxp3+ cells were highly represented in the liver infiltrates, they were not related to liver damage. In contrast, our results suggested that intrahepatic IL-17+ cells mediated fibrosis severity both in chronic HBV and HCV infections. Although the immune scenario against both viral infections is supposed to be different, the IL-17+ and Foxp3+ liver populations showed a similar behavior in both infective conditions