Transcription factor Foxp1 exerts essential cell-intrinsic regulation of the quiescence of naive T cells.

Academic Article

Abstract

  • The molecular mechanisms that underlie T cell quiescence are poorly understood. Here we report that mature naive CD8(+) T cells lacking the transcription factor Foxp1 gained effector phenotype and function and proliferated directly in response to interleukin 7 (IL-7) in vitro. Foxp1 repressed expression of the IL-7 receptor α-chain (IL-7Rα) by antagonizing Foxo1 and negatively regulated signaling by the kinases MEK and Erk. Acute deletion of Foxp1 induced naive T cells to gain an effector phenotype and proliferate in lympho-replete mice. Foxp1-deficient naive CD8(+) T cells proliferated even in lymphopenic mice deficient in major histocompatibility complex class I. Our results demonstrate that Foxp1 exerts essential cell-intrinsic regulation of naive T cell quiescence, providing direct evidence that lymphocyte quiescence is achieved through actively maintained mechanisms that include transcriptional regulation.
  • Authors

    Keywords

  • Animals, Butadienes, CD8-Positive T-Lymphocytes, Cell Proliferation, Cells, Cultured, Enzyme Inhibitors, Extracellular Signal-Regulated MAP Kinases, Female, Flow Cytometry, Forkhead Box Protein O1, Forkhead Transcription Factors, Gene Expression Regulation, Imidazoles, Immunoblotting, Interleukin-7, MAP Kinase Kinase Kinases, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Nitriles, Protein Binding, Pyridines, Receptors, Interleukin-7, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes
  • Digital Object Identifier (doi)

    Author List

  • Feng X; Wang H; Takata H; Day TJ; Willen J; Hu H
  • Start Page

  • 544
  • End Page

  • 550
  • Volume

  • 12
  • Issue

  • 6