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FOXO transcription factors throughout T cell biology

2012; Nature Portfolio; Volume: 12; Issue: 9 Linguagem: Inglês

10.1038/nri3278

1474-1741

Stephen Μ. Hedrick, Rodrigo Hess Michelini, Andrew L. Doedens, Ananda W. Goldrath, Erica L. Stone,

T-cell and B-cell Immunology

Forkhead box O (FOXO) transcription factors have many diverse physiological functions and regulate gene-expression programmes that are involved in immunity, metabolism and oncogenesis. This Review discusses how FOXO proteins integrate different environmental signals in order to regulate T cell differentiation and functions in a context-dependent manner. The outcome of an infection with any given pathogen varies according to the dosage and route of infection, but, in addition, the physiological state of the host can determine the efficacy of clearance, the severity of infection and the extent of immunopathology. Here we propose that the forkhead box O (FOXO) transcription factor family — which is central to the integration of growth factor signalling, oxidative stress and inflammation — provides connections between physical well-being and the form and magnitude of an immune response. We present a case that FOXO transcription factors guide T cell differentiation and function in a context-driven manner, and might provide a link between metabolism and immunity.