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Foxp1 controls naive CD8+ T cell quiescence by simultaneously repressing key pathways in cellular metabolism and cell cycle progression #MMPMID27001958
Wei H; Geng J; Shi B; Liu Z; Wang YH; Stevens AC; Sprout SL; Yao M; Wang H; Hu H
J Immunol 2016[May]; 196 (9): 3537-41 PMID27001958show ga
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. Here we report that the deletion of Foxp1 in naive CD8+ T cells leads to enhanced activation of PI3K/Akt/mTOR signaling pathway and its downstream cell growth and metabolism targets in response to IL-7. We found that Foxp1 directly regulates Pik3ip1, a negative regulator of PI3K. In addition, 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 (Rb). 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.