Small intestinal lamina propria immune cells dyshomeostasis is associated with alcoholic steatohepatitis in the mouse

Abstract The intestine represents the largest compartment of the immune system. Small intestinal lamina propria (SILP) immune processes are increasingly implicated in controlling disease development in the body. We have shown that reduction of tight junction proteins, system dysbiosis, and endotoxins translocation to the liver accounts for alcohol-induced steatohepatitis. However, the underlying mechanisms are still unclear. The present study investigated the effects of SILP antigen presenting cells dyshomeostasis on the pathogenesis of alcoholic steatohepatitis. Alcohol-induced liver inflammation was analyzed by inflammatory immune cells infiltration and proinflammatory cytokine gene expression. Chronic alcohol exposure (8 weeks) not only cause enteric dysbiosis but also increased plasma endotoxins (LPS) levels. The frequency of CD64-CD45+MHCII+CD11chi dendritic cells and CD64+F4/80+CD11b+ macrophage were both increased in SILP after chronic alcohol exposure. Further analysis demonstrated that alcohol exposure differently regulates CD103+ and CD103- dendritic cells subsets ratio. Intestinal IL-12p70 was significantly decreased after alcohol exposure. alcohol feeding also increased th2 cells but decreased th1 cells in SILP. The present study demonstrated that small intestinal immune cells activation may account for alcohol-induced dysbiosis, and thereby being a pathophysiological factor in the development of alcoholic steatohepatitis.