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

Immunity | Mar 20, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19285438

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.

Pubmed ID: 19285438 RIS Download

Mesh terms: Animals | Base Sequence | Cell Cycle Proteins | Cells, Cultured | Cloning, Molecular | F-Box Proteins | Flow Cytometry | Forkhead Transcription Factors | Homeostasis | Humans | Immune Tolerance | Mice | Molecular Sequence Data | Nerve Tissue Proteins | Receptors, Interleukin-7 | SKP Cullin F-Box Protein Ligases | T-Lymphocytes

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Associated grants

  • Agency: NIDDK NIH HHS, Id: DK51665
  • Agency: PHS HHS, Id: K01
  • Agency: NIAMS NIH HHS, Id: K01 AR053595
  • Agency: NIAMS NIH HHS, Id: K01 AR053595-01
  • Agency: NIAMS NIH HHS, Id: K01 AR053595-02
  • Agency: NIAMS NIH HHS, Id: K01 AR053595-03

Mouse Genome Informatics (Data, Gene Annotation)

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