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

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

Authors

  • Ouyang W
  • Beckett O
  • Flavell RA
  • Li MO

Journal

Immunity

Publication Data

March 20, 2009

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

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