n3-polyunsaturated fatty acids modified the hepatic immune cell phenotype in response to ethanol challenge in mice 2470

Description Ethanol (EtOH)-induced alterations in hepatic immune cell phenotypes and function play a critical role in the pathogenesis of alcohol-associated liver disease (ALD). n3-polyunsaturated fatty acids (PUFAs) are known to have a broad impact on the immune system; however, their effects in the context of alcohol exposure remain under-investigated. In this study, we examined the effects of n3 PUFA endogenous enrichment on hepatic immune cell populations in an animal model of ALD. Compared to EtOH-treated wild type (WT) mice, animals with endogenous n3 PUFA enrichment (transgenic fat-1 mice) exhibited a reduction in the pro-inflammatory M1 phenotype of liver-resident macrophages, Kupffer Cells (KCs), with no significant changes in M2 KCs, indicating a shift away from a pro-inflammatory KC phenotype. Additionally, fat-1 EtOH-treated mice showed an increase in liver anti-inflammatory regulatory T cells, a cell type which is critical for maintaining immune homeostasis and self-tolerance, as well as blocking pro-inflammatory signals. Further, there were trending increases in other liver immune cell populations in EtOH-treated fat-1 compared to WT mice, including natural killer cells and conventional T cells. These findings suggest that n3-PUFAs can modulate both innate and adaptive immunity in the liver, which may influence the overall inflammatory responses, and ultimately contribute to the attenuation of EtOH-induced liver inflammation and injury. Funding Sources Supported by NIH P50 AA024337-01 Topic Categories Immune Mechanisms of Human Disease (HUM)