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An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance.

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.

SUBMITTER: Ouyang W

PROVIDER: S-EPMC2692529 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance.

Ouyang Weiming W Beckett Omar O Flavell Richard A RA Li Ming O MO

Immunity 20090312 3

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 peripher ...[more]

PMID: 19285438

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