An Essential Role of the Forkhead-Box Transcription Factor Foxo1 in Control of T Cell Homeostasis and Tolerance

Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Immunity (Impact Factor: 19.75). 04/2009; 30(3):358-71. DOI: 10.1016/j.immuni.2009.02.003
Source: PubMed

ABSTRACT Members of the Forkhead box O (Foxo) family of transcription factors are key regulators of cellular responses, but their function in the immune system remains incompletely understood. Here we showed that T cell-specific deletion of Foxo1 gene in mice led to spontaneous T cell activation, effector T cell differentiation, autoantibody production, and the induction of inflammatory bowel disease in a transfer model. In addition, Foxo1 was critical for the maintenance of naive T cells in the peripheral lymphoid organs. Transcriptome analyses of T cells identified Foxo1-regulated genes encoding, among others, cell-surface molecules, signaling proteins, and nuclear factors that control gene expression. Functional studies validated interleukin-7 receptor-alpha as a Foxo1 target gene essential for Foxo1 maintenance of naive T cells. These findings reveal crucial functions of Foxo1-dependent transcription in control of T cell homeostasis and tolerance.

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May 16, 2014