Estrogen related receptor-α is a global metabolic and fate determinant for T lymphocytes (139.8)
| Autor: | Ryan Michalek, Sarah Jacobs, Ching-yi Chang, Olga Ilkayeva, Nancie Maciver, Russell Jones, Vincent Giguere, Donald McDonnell, Jeffrey Rathmell |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 184:139.8-139.8 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | T lymphocyte activation initiates rapid cell growth and proliferation that is fueled by increased glucose metabolism. Molecular factors contributing to this transition and how metabolism impacts immunity, however, have remained uncertain. We have uncovered a critical role for the orphan nuclear receptor Estrogen Related Receptor-alpha (ERRα) in this metabolic program and T cell differentiation. In the absence of ERRα activated T cells failed to elevate glucose metabolism, resulting in diminished growth, proliferation, and effector function. The generation of inducible regulatory T cells was also selectively inhibited in the absence of ERRα. Metabolomic analysis demonstrated that the loss of ERRα promoted a shift from glycolytic metabolism to lipid oxidation. Importantly, defects in growth and differentiation in the absence of ERRα were overcome by addition of excess lipids as an alternate mitochondrial fuel. Furthermore, induction of lipid metabolism in T cells selectively promoted the generation of regulatory T cells in vitro and in vivo and suppressed the differentiation of effector Th17 cells in vitro. Together, these results demonstrate that ERRα is essential to drive glucose metabolism of activated T cells and that metabolic phenotype can strongly influence T cell differentiation. |
| Databáze: | OpenAIRE |
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