Abstract
Reactive oxygen species (ROS) contribute as second messengers in immune cells but little is known about their role in NKT cell function. We found that ROS levels in NKT cells dramatically increased compared to T cells in the spleen and liver but not in thymus or adipose tissues. Freshly isolated NKT cells produced ROS using primarily NADPH oxidases not mitochondria. Accordingly, NKT cells were susceptible to oxidative stress. ROS levels regulate the inflammatory function of NKT cells. ROS-high NKT cells had more NKT1 and NKT17 subsets but fewer NKT2 cells than ROS-low cells. Antioxidant treatment or activation of NKT cells resulted in reduced ROS, IFN-γ+ and IL-17+ cells. These characteristics are regulated by PLZF as evidenced by low ROS in NKT cells from PLZF haplo-deficient mice and highly elevated ROS in CD4 T cells from mice ectopically-expressing PLZF. Together, our study reveals that ROS regulate NKT cell function through PLZF.