Cutting edge: Foxp1 controls naive CD8+ T cell quiescence by simultaneously repressing key pathways in cellular metabolism and cell cycle progression
The Journal of Immunology, 2016•journals.aai.org
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 …
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 …
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.
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