Cutting edge: Foxp1 controls naive CD8 + t cell quiescence by simultaneously repressing key pathways in cellular metabolism and cell cycle progression

Academic Article

Abstract

  • Previously we have shown that transcription factor Foxp1 plays an essential role in maintaining naive T cell quiescence; in the absence of Foxp1, mature naive CD8 + T cells proliferate in direct response to homeostatic cytokine IL-7. In this study, we report that the deletion of Foxp1 in naive CD8 + T cells leads to enhanced activation of the PI3K/Akt/mammalian target of rapamycin signaling pathway and its downstream cell growth and metabolism targets in response to IL-7. We found that Foxp1 directly regulates PI3K interacting protein 1, a negative regulator of PI3K. Additionally, we found that deletion of Foxp1 in naive CD8 + T cells results in increased expression levels of E2fs, the critical components for cell cycle progression and proliferation, in a manner that is not associated with increased phosphorylation of retinoblastoma protein. Taken together, our studies suggest that Foxp1 enforces naive CD8 + T cell quiescence by simultaneously repressing key pathways in both cellular metabolism and cell cycle progression.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Wei H; Geng J; Shi B; Liu Z; Wang YH; Stevens AC; Sprout SL; Yao M; Wang H; Hu H
  • Start Page

  • 3537
  • End Page

  • 3541
  • Volume

  • 196
  • Issue

  • 9