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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B226
Abstract ID: 4652

Presenting Author:
Afrooz Dabbaghizadeh , Postdoc researcher at Ctr. Hosp. de Univ. de Montréal, Univ. de Montréal

Abstract:

Liver fibrosis due to various aetiologies is a major health problem. The type 3 inflammatory cytokine IL17 is enriched in livers with advanced fibrosis underscoring its profibrogenic role and suggesting that it as a therapeutic target. The goal of this study is to test the efficacy of novel pharmacological compounds targeting IL17 production in the context of the CCl4 mouse model of chronic toxic liver injury. C57BL/6 mice received two weekly injections of CCl4 (0.5 ml/Kg) for 4 weeks. As of week 3, mice were treated with two novel pharmacological inhibitors of IL17A or GSK805 as a positive control (10 mg/Kg/day). Treatment with the inhibitors led to reduction in the infiltration of immune cells around the portal and central veins significant reduction in the serum transaminases ALT and AST (p<0.05) as markers of liver injury. Inhibitors also reduced the number of infiltrating intrahepatic lymphocytes (CD3+CD4+and CD8+, γd, p<0.05) and myeloid (CD11b+) cells (p=0.04) with a trend towards reduction of neutrophils (p=0.09).  Importantly, we observed significant reduction in IL17A production by CD4+ and γδ – T cells (p<0.01 and p<0.001, respectively). Finally, the inhibitors reduced the expression of the profibrogenic genes (Col1a1, Acta, Loxl2 and Tgfβ) (p<0.001) and reduced collagen deposition as measured by Picro sirius red area (p<0.05). In conclusion, our data suggest that inhibition of the IL17 pathway is a viable therapeutic strategy for liver fibrosis.