Liver Th17/ Treg interplay related to pathogenesis of both chronic HBV and HCV infection

GIADANS C; RÍOS D; FRIAS S; HADDAD L; DE MATTEO E; MULLEN E; CASCIATO P; AMEIGEIRAS B; BRODERSEN C; GALDAME O; FLICHMAN D; VALVA P; MARIA VICTORIA PRECIADO

Viena

Congreso; European Congress of Clinical Microbiology and Infectious Diseases; 2017

Background: Inviralchronichepatitis,theimmunesystemisinvolvedinliverdamage,buttheroleofeachimmunecellpopulationisstillunknown.ItwassuggestedthatThelper17(Th17)andregulatoryTcells(Treg)balanceiscriticalinthepathogenesis;however,itsregulationwaspoorlyunderstood.ThestudyaimwastoexaminetheroleofTh17andTregsinchronicdiseaseofbothHepatitisBvirus(HBV)andHepatitisCvirus(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 Knodells coring system(HistologicalActivityIndex,HAI) and METAVIR. The results were evaluated in the context of liver damage.Results: Both studied populations were observed inportal/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/severeHAI;HCV:62% significant fibrosis,75%Moderate/severeHAI;pfibrosis=0.34,Fishertest,pHAI=0.38,Chi-squaretest).IL17+ cells depicted positive association with fibrosis severity in both HBV (p=0.004,Student-test) and HCV (p=0.013,Mann-Whitneytest) cases ;while no association with hepatitis was observed in any case. Although its high frequency,Foxp3+cells showed no association with neither hepatitis nor fibrosis.Finally,the IL17+/Foxp3+ cell ratio was associated with advanced fibrosis(p=0.024,Mann-Whitneytest) only in HCV cases.Conclusion: The pathogenesis of viral hepatitis is a complex process involving several immunecell 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 intrahepaticIL-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.