RT Journal Article
SR Electronic
T1 Reactive Oxygen Species Regulate the Inflammatory Function of NKT Cells through Promyelocytic Leukemia Zinc Finger
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 122390
DO 10.1101/122390
A1 Yeung-Hyen Kim
A1 Ajay Kumar
A1 Cheong-Hee Chang
A1 Kalyani Pyaram
YR 2017
UL http://biorxiv.org/content/early/2017/04/11/122390.abstract
AB 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.