Liver X receptors regulate natural killer T cell population and antitumor activity in the liver of mice

The nuclear receptors liver X receptor alpha (LXR alpha) and LXR beta are lipid sensors that regulate lipid metabolism and immunity. Natural killer T (NKT) cells, a T cell subset expressing surface markers of both natural killer cells and T lymphocytes and involved in antitumor immunity, are another abundant immune cell type in the liver. The potential function of the metabolic regulators LXR alpha/beta in hepatic NKT cells remains unknown. In this study, we examined the role of LXR alpha and LXR beta in NKT cells using mice deficient for LXR alpha and/or LXR beta, and found that hepatic invariant NKT (iNKT) cells are drastically decreased in LXR alpha/beta-KO mice. Cytokine production stimulated by the iNKT cell activator alpha-galactosylceramide was impaired in LXR alpha/beta-KO hepatic mononuclear cells and in LXR alpha/beta-KO mice. iNKT cell-mediated antitumor effect was also disturbed in LXR alpha/beta-KO mice. LXR alpha/beta-KO mice transplanted with wild-type bone marrow showed decreased iNKT cells in the liver and spleen. The thymus of LXR alpha/beta-KO mice showed a decreased population of iNKT cells. In conclusion, LXR alpha and LXR beta are essential for NKT cell-mediated immunity, such as cytokine production and hepatic antitumor activity, and are involved in NKT cell development in immune tissues, such as the thymus.

Automated summary

The study reveals that LXR alpha and LXR beta play essential roles in NKT cell-mediated immunity, such as cytokine production and hepatic antitumor activity, and are involved in NKT cell development in immune tissues, such as the thymus.