scholarly journals Reactive Oxygen Species Regulate the Inflammatory Function of NKT Cells through Promyelocytic Leukemia Zinc Finger

2017 ◽  
Vol 199 (10) ◽  
pp. 3478-3487 ◽  
Author(s):  
Yeung-Hyen Kim ◽  
Ajay Kumar ◽  
Cheong-Hee Chang ◽  
Kalyani Pyaram
Keyword(s):  
Reactive Oxygen Species ◽  
Zinc Finger ◽  
Reactive Oxygen ◽  
Nkt Cells ◽  
Promyelocytic Leukemia ◽  
Oxygen Species ◽  
Promyelocytic Leukemia Zinc Finger

scholarly journals Reactive Oxygen Species Regulate the Inflammatory Function of NKT Cells through Promyelocytic Leukemia Zinc Finger

2017 ◽  
Author(s):  
Yeung-Hyen Kim ◽  
Ajay Kumar ◽  
Cheong-Hee Chang ◽  
Kalyani Pyaram
Keyword(s):  
Reactive Oxygen Species ◽  
T Cells ◽  
Zinc Finger ◽  
Reactive Oxygen ◽  
Nkt Cells ◽  
Promyelocytic Leukemia ◽  
Oxygen Species ◽  
Nkt Cell ◽  
Adipose Tissues ◽  
Promyelocytic Leukemia Zinc Finger

AbstractReactive oxygen species (ROS) are byproducts of aerobic metabolism and contribute to both physiological and pathological conditions as second messengers. ROS are essential for antigen specific activation of T cells, but little is known about what role ROS play in NKT cells. In the current study, we investigated the role of ROS in NKT cell function. We found that ROS levels are similar among CD4, CD8 and NKT cell subsets in the thymus. However, NKT cells, but neither CD4 nor CD8 T cells, showed dramatically increased ROS in the spleen and liver but not in adipose tissues. ROS in the peripheral NKT cells were primarily produced by NADPH oxidases not mitochondria. Accordingly, ROS-high NKT cells were susceptible to oxidative stress and underwent apoptotic cell death. Furthermore, ROS play an important role in regulating the inflammatory function of NKT cells because antioxidant treatment of NKT cells showed reduced frequencies of IFN-γ+ and IL-17+ cells. In line with this, freshly isolated ROS-high NKT cells had more NKT1 and NKT17 cells but less NKT2 than ROS-low cells. These characteristics are regulated by promyelocytic leukemia zinc finger (PLZF) as evidenced by low ROS in NKT cells from PLZF haplodeficient mice and also from adipose tissues that do not express PLZF. Conversely, ROS were highly elevated in CD4 T cells from mice ectopically expressing PLZF. Together, our study revealed for the first time that ROS regulate NKT cell functions through PLZF.

scholarly journals Diabetes Mellitus Directs NKT Cells Toward Type 2 and Regulatory Phenotype / Diabetes Melitus Usmerava Diferencijaciju NKT Celija U Pravcu Tip 2 I Regulatornog Fenotipa

2016 ◽  
Vol 17 (1) ◽  
pp. 35-41
Author(s):  
Nevena Gajovic ◽  
Ivan Jovanovic ◽  
Aleksandar Ilic ◽  
Nevena Jeremic ◽  
Vladimir Jakovljevic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Nkt Cells ◽  
Diabetic Patients ◽  
Oxygen Species ◽  
Chronic Disorder ◽  
Functional Phenotype

Abstract Diabetes mellitus is chronic disorder characterized by hyperglycaemia. Hyperglycaemia induces mitochondrial dysfunction, enhances oxidative stress and thus promotes reactive oxygen species (ROS) production. Earlier studies suggested that reactive oxygen species (ROS) are involved in the pathogenesis of many diseases. Previous studies have revealed that hyperglycaemia changes the functional phenotype of monocytes, macrophages, neutrophils, NK cells and CD8+ T cells. The aim of this study was to investigate whether diabetes affects the functional phenotype of NKT cells. Diabetes mellitus was induced in BALB/c mice by intraperitoneal injection of streptozotocin at a single dose of 170 mg/kg body weight. The number and functional phenotype of splenic NKT cells was assessed by fl ow cytometry, 28 days after diabetes induction. The diabetic condition facilitated the production of antioxidant enzymes, including catalase (p<0.05) and superoxide dismutase. Hyperglycaemia enhanced oxidative stress and thus decreased the number of splenic NKT cells but did not change the percentage of splenic CD3+CD49+ NKT cells that express the activatory receptor NKP46 or produce IFN-γ. However, hyperglycaemia increased the frequency of splenic NKT cells that express KLRG-1 and produce TGF-β, IL-4, and IL-5, and it decreased the frequency of IL-17+ NKT cells. Our study indicates that diabetes mellitus induces oxidative stress and switches the functional phenotype of NKT cells towards type 2 (IL-4 and IL-5 producing NKTs) and regulatory (TGF-β Thproducing NKTs) phenotypes. These findings are correlated with the clinical observation in humans that diabetic patients are more prone to infections and tumours.

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