<abstract xmlns="http://www.w3.org/1999/xhtml"> 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&lt;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. </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.

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

Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Serbia

Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Serbia, Svetozara Markovica 69, 34000 Kragujevac, Serbia, Tel +38134306800, Fax. +38134306800112

Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Serbia

Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia

Experimental and Applied Biomedical Research (EABR)

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Diabetes mellitus is chronic disorder characterized by hyperglycaemia. Hyperglycaemia induces mitochondrial dysfunction, enhances oxidative stress and thus...

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

Published Online: Apr 14, 2016

Page range: 35 - 41

Received: Dec 17, 2015

Accepted: Jan 05, 2016

DOI: https://doi.org/10.1515/sjecr-2016-0005

Keywords
diabetes, hyperglycaemia, oxidative stress, NKT cells

© 2016

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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

Published Online: Apr 14, 2016

Page range: 35 - 41

Received: Dec 17, 2015

Accepted: Jan 05, 2016

DOI: https://doi.org/10.1515/sjecr-2016-0005

Keywordsdiabetes, hyperglycaemia, oxidative stress, NKT cells

© 2016

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Keywords
diabetes, hyperglycaemia, oxidative stress, NKT cells