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

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.

SUBMITTER: Feng X

PROVIDER: S-EPMC3631322 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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

Feng Xiaoming X Wang Haikun H Takata Hiroshi H Day Timothy J TJ Willen Jessica J Hu Hui H

Nature immunology 20110501 6

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 phenot ...[more]

PMID: 21532575

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