Metabolic regulation of CD4+ T cells by Estrogen Related Receptor-α modulates autoimmune and allergic disease (123.48)
| Autor: | Ryan Michalek, Valerie Gerriets, Amanda Nichols, Makoto Inoue, Barbara Theriot, Vincent Giguere, Donald McDonnell, Mari Shinohara, Julia Walker, Jeffrey Rathmell |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:123.48-123.48 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Upon activation, naïve CD4+ T cells differentiate into effector (Teff) subsets that provide protective immunity or inducible regulatory (Treg) subsets which balance inappropriate inflammation and autoimmunity. Consistent with distinct immunological roles, Teff and Treg utilize specialized metabolic programs for specification and function with Treg increasing lipid oxidation and Teff dependent on glucose metabolism. We have identified the nuclear receptor estrogen related receptor-α (ERRα) as a critical regulator of metabolic gene expression required for Teff. Here, we demonstrate through the use of an experimental autoimmune encephalomyelitis model that ERRα contributes to the severity of autoimmune disease as limited glucose metabolism in the absence of ERRα selectively diminished Th17, but not Treg generation. ERRα contributed to inappropriate inflammation as Teff glucose metabolism, expansion, and function were reduced in ERRα-/- mice and in siRNA treated human CD4+ T cells. Additionally, elevated ERRα expression and glycolytic metabolism were also observed in a murine model of asthma and from lavage fluid of asthmatic patients. Importantly, pharmacological inhibition of ERRα following an aerosol response alleviated airway inflammation, demonstrating a metabolic requirement for ERRα in Teff maintenance. Thus, ERRα is a selective transcriptional regulator of Teff metabolism that may provide a metabolic means to modulate immunity. |
| Databáze: | OpenAIRE |
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