Cd8+t cells regulate liver injury in obesity-related nonalcoholic fatty liver disease.

CD8+T CELLS REGULATE LIVER INJURY IN OBESITY-RELATED NONALCOHOLIC FATTY LIVER DISEASE. Am J Physiol Gastrointest Liver Physiol. 2019 Nov 11;: Authors: Breuer DA, Pacheco MC, Washington MK, Montgomery SA, Hasty AH, Kennedy AJ Abstract Nonalcoholic steatohepatitis (NASH) has increased in Western countries due to the prevalence of obesity. Current interests are aimed at identifying the type and function of immune cells that infiltrate the liver and key factors responsible for mediating their recruitment and activation in NASH. We investigate the function and phenotype of CD8+T cells under obese and non-obese NASH conditions. We found an elevation in CD8 staining in livers from obese human subjects with NASH and cirrhosis that positively correlated with a-smooth muscle actin, a marker of hepatic stellate cell (HSC) activation. CD8+T-cells were elevated 3.5-fold in the livers of obese and hyperlipidemic NASH mice compared to obese hepatic steatosis mice. Isolated hepatic CD8+T-cells from these mice expressed a cytotoxic IL-10 expressing phenotype and depletion of CD8+T cells led to significant reductions in hepatic inflammation, HSC activation, and macrophage accumulation. Furthermore, hepatic CD8+T cells from obese and hyperlipidemic NASH mice activated HSCs in vitroand in vivo. Interestingly, in the lean NASH mouse model, depletion and knockdown of CD8+T cells did not impact liver inflammation or HSC activation. We demonstrate that unde...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research