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

Xiaoming Feng, Haikun Wang, Hiroshi Takata, Timothy J. Day, Jessica Willen, Hui Hu

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

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 ±-chain (IL-7R±) 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.

Original languageEnglish (US)
Pages (from-to)544-550
Number of pages7
JournalNature Immunology
Volume12
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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