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Manipulation of metabolism of Th is able to induce differentiation of Th in vitro, saturated and unsaturated fatty acids are able to induce Th1 and Th17.
In this study by Dr. R. Masnsouri effect of metabolism on Th differentiation has been examined. Because of an important role of metabolic reprogramming of Th cell after activation, from catabolism in rest state to anabolism in active state, it seems that access or lack of access of micro or macro elements may direct Th subsets differentiation.
“Before activation Th cells catalyzed glucose in TCA and produced high level of energy, whilst after activation they use glycolysis to gain energy and critical backbones for DNA, protein and fatty acids synthesis.” Hence fatty acids as an important element of our diet and as source of energy has been chosen to manipulate Th cells metabolism and consequent differentiation.
In fact, now it is clear that T effector subsets (Th1, Th2 and Th17) are glycolytic and rely on glucose as source of energy whilst T regulatory is oxidative, mainly fatty acid oxidation. On the other hand, because T effectors are glycolytic, mTOR play a critical role in their differentiation. It means that by mTOR inhibition, T effector differentiation will be failed. Hence it could be possible that by adding fatty acid to T-cell culture, T regulatory can be induced and mTOR expression suppressed.
Our results show that 1mM palmitic/oleic acid not only cannot induce T regulatory differentiation but also Th1 and Th17 have been induced. According to Th1 and Th17 induction mTOR also has been up-regulated. Because mTORC1 control differentiation of Th1 and Th17 and mTORC2 differentiate Th2, our results can be shown that mTORC1 active by exogenous fatty acids.
Our results do not support some past studies findings; saturated fatty acids have pro-inflammatory effects and unsaturated fatty acids are anti-inflammatory. Our data shows that palmitic acid (as saturated F.A), oleic acid (unsaturated F.A) and their combination have same effects on Th differentiation. It need to be investigated that biochemical pathway for using these fatty acids have cross talk that may cause similar results. About oleic acid it should be mentioned that, it is omega-9 unsaturated fatty acids and it can be logical that why its results differ from omega-3 saturated fatty acids with clear anti-inflammatory effects. By designing further studies it can be accessible that unique media formulate for specific Th differentiation. These cells may use for T-cell therapy of autoimmune diseases.
Reza Mansouri MD-PhD Assistant Professor Department of Immunology Faculty of Medicine Shahid Sadoughi University of Medical Sciences Safaieye, Bo-Ali street Yazd/IranAissouda Hossein zade Graduate student of immunology, Department of Immunology Faculty of Medicine Shahid Sadoughi University of Medical Sciences Safaieye, Bo-Ali street Yazd/Iran Maryam Moogooei Graduate student of immunology, Department of Immunology Faculty of Medicine Shahid Sadoughi University of Medical Sciences Safaieye, Bo-Ali street Yazd/Iran Shayan Mostafaei Ph.D. Student, Department of Biostatistics, Faculty of medical sciences, Tarbiat Modares University, Tehran, Iran Hossein Rahavi instructor of Department of Immunology Faculty of Medicine Shahid Sadoughi University of Medical Sciences Safaieye, Bo-Ali street Yazd/Iran Sepideh Soukhtezari Department of medical biotechnology, Tarbiat Modares Univesity, Tehran, Iran Mojgan Ghaedi Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran