Metabolism of murine TH17 cells: Impact on cell fate and function |
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| Authors: | Ran Wang Laura A. Solt |
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| Affiliation: | Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, USA |
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| Abstract: | An effective adaptive immune response relies on the ability of lymphocytes to rapidly act upon a variety of insults. In T lymphocytes, this response includes cell growth, clonal expansion, differentiation, and cytokine production, all of which place a significant energy burden on the cell. Recent evidence shows that T‐cell metabolic reprogramming is an essential component of the adaptive immune response and specific metabolic pathways dictate T‐cell fate decisions, including the development of TH17 versus T regulatory (Treg) cells. TH17 cells have garnered significant attention due to their roles in the pathology of immune‐mediated inflammatory diseases. Attempts to characterize TH17 cells have demonstrated that they are highly dynamic, adjusting their function to environmental cues, which dictate their metabolic program. In this review, we highlight recent data demonstrating the impact of cellular metabolism on the TH17/Treg balance and present factors that mediate TH17‐cell metabolism. Some examples of these include the differential impact of the mTOR signaling complexes on T‐helper‐cell differentiation, hypoxia inducible factor 1 alpha (HIF1α) promotion of glycolysis to favor TH17‐cell development, and ACC1‐dependent de novo fatty acid synthesis favoring TH17‐cell development over Treg cells. Finally, we discuss the potential therapeutic options and the implications of modulating TH17‐cell metabolism for the treatment of TH17‐mediated diseases. |
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| Keywords: | Fatty acid ⋅ HIF1α ⋅ Glycolysis ⋅ mTOR ⋅ RORγ t ⋅ TH17/Treg balance |
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