We read with interest the article by Ma et al. on how a high-fat diet reduced regulatory T cells (Tregs) in liver and influenced susceptibility to endotoxin-induced liver injury. 1 This interesting finding may also explain a previous report on increased sensitivity in mice with fatty liver to concanavalin A-induced hepatitis. 2 The authors attributed the mechanism of Treg loss to oxidative stressinduced apoptosis.
Recently, several agents were found that regulate Treg survival and function. Among them, leptin, a neuroendocrine and immune mediator, 3 acts as a negative signal for the proliferation of Tregs. 4 The suppressive effect of leptin on Tregs was mediated by the modulation of cyclin-dependent kinase inhibitor p27 (p27 kip1 ) levels and phosphorylation of extracellular-related kinase 1 (ERK1) and ERK2.
Serum leptin levels can be considered as a signal to the body of its energy reserves. 5 Previous studies have clearly shown that serum leptin levels correlate directly with the severity of hepatic steatosis. 6 Therefore, based on these findings, it will be interesting and important to verify the role elevated leptin levels play in Treg loss in mice with fatty livers.
In addition, a significant increase of the percentage of peripheral Tregs was observed in mice with a genetic deficiency of leptin (ob/ob mice). 4 One of the most prominent phenotypes of ob/ob mice was fatty liver. So, further research should be carried out to determine the percentage of Tregs in liver of ob/ob mice. These studies will improve our knowledge about the interaction between hepatocytes and immune cells in the liver.