OXIDANT STRESS AND ADAPTIVE IMMUNITY IN ASH AND NASH

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Albano E, Bruzzì S, Sutti S.

Dept of Health Sciences, University “A. Avogadro” of East Piedmont, Novara Italy.

It is well established that chronic hepatic inflammation represents the main driving force in the evolution to fibrosis/cirrhosis of both alcoholic (ASH) and nonalcoholic (NASH) steatohepatitis. So far, innate immune mechanisms have been recognized as the main responsible in supporting inflammatory processes in steatohepatitis. However, growing evidence points on the possible role of adaptive immunity as an additional factor in promoting hepatic inflammation in ASH and NASH. In fact, patient with ASH and NASH, but not those with steatosis only, are characterized by the presence of circulating antibodies and lymphocyte-mediated responses triggered by antigens originating from oxidative stress. Similar immune responses are also detectable in experimental models of ASH and NASH and interference with either oxidative stress or the functions of either helper CD4+ and effector CD8+ T-lymphocytes ameliorates steatohepatitis. In these settings, T-lymphocytes contribute to sustain lobular inflammation and fibrosis by stimulating macrophage activation as well as by promoting natural killer T-cell (NKT) recruitment. Present data also suggest that alterations in regulatory T-cell (Treg) homeostasis and hepatic dendritic cell activation have a role in triggering immune responses during the evolution of steatohepatitis. Clarify the contribution of adaptive immunity in ASH and NASH will open new scenarios on the factors responsible for the inter-individual variability in the disease progression to fibrosis and will provide the rationale for novel treatments based on the application of a wide array of molecules already being used in other conditions characterized by impaired immune regulation or autoimmunity.

Invited presentation to the 11th International Symposium on ALPD and Cirrhosis

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