ADIPOSE TISSUE-LIVER AXIS: INVOLVEMENT OF THE TH17 PATHWAY IN THE PROGRESSION OF HUMAN NAFLD

CHACKELEVICIUS CARLA; GIRAUDI PABLO; GAMBARO SABRINA ELIANA; PALMISANO S; GIURICIN M.; DE MANZINI N.; BONAZZA D; ZANCONATTI F.; TIRIBELLI CLAUDIO; ROSSO NATALIA

Barcelona

Congreso; The International Liver Congress? 2016, EASL; 2016

European Association for the Study of the Liver, EASL

Background and Aims: Chronic inflammation is a key player in theprogression of NAFLD/NASH. Morbid obesity is a known risk factor ofNAFLD. It has been found that adipose tissue from obese patients hashigher   CD4   Th17   cell   content   than   normal   subjects.   Thedifferentiation of naïve CD4 T cells into Th17 cells is triggered byTGFβ, IL6 and IL1β, which induce the expression of the transcriptionfactor Orphan Nuclear Receptor (RORC). After stimulation Th17 cellssecrete IL-17 that binding IL-17RA, propagates a cascade of eventsthat lead to neutrophil recruitment, inflammation and host defense.Periostin,  one  end-product  of  this  pathway,  is  a  secretory  celladhesion  protein  recently  involved  in  pathogenesis  of  fibrosisobserved both in vitro and in vivo. The aim of the present study isto explore the Th17 pathway in human NAFLD.Methods: Prospectively we included in the study 14 morbidly obesesubjects undergoing bariatric surgery (7 men and 7 women with amean age of 43 years (19?60), mean BMI 46.5). We analyzed mRNAexpression of the Th17 pathway (RORC, IL-17, IL-17RA) and Periostin(POSTN) in liver and visceral adipose tissue biopsies. According to thehistological status, patients were divided according Brunt?s score ofliver fibrosis F0 (n = 2), F1 (n = 5), F2 (n = 7). Data was correlated withthe  expression  of  other  markers  involved  in  inflammation  (IL1β;TNFα, VEGFA, IL8, IL6) and fibrosis (TGFβ; αSMA, COL1A1).Results: We found that adipose tissue of patients with F2 stage ofliver fibrosis shows an overexpression of RORC (p < 0.05) and IL-17RA(p < 0.05) genes respect to F0 group whereas IL17 was overexpressedonly in F1 (p < 0.001). Moreover, hepatic gene expression of RORC(p < 0.05), IL17RA (p < 0.05) and Periostin (p < 0.05) was higher in theF1 and F2 group compared with the F0. No changes were observed inIL17 hepatic gene expression. All together these results are in linewith those observed for inflammation IL1β; TNFα, VEGFA, IL8 andfibrosis markers TGFβ; αSMA, COL1A1.Conclusions: IL17 might be a key factor involved in the pathogenesisof liver inflammation and progression to fibrosis. Adipose tissue playsan important role as a source of IL17 conferring higher risk of NAFLDto obese patients. Our preliminary data, in line with other reportedstudies, suggests that liver Periostin could be involved in hepaticfibrogenesis.CMC is supported by MAE, PJG by Fondazione Umberto Veronesi, SEGby Progetto 297 nutrizione. To U05SPFRA14 - FRA 2014 (CdA dd.19.12.2014) and by FIF grant.