Noc4L-Mediated Ribosome Biogenesis Controls Activation of Regulatory and Conventional T Cells

Abstract

Regulatory Tcell (Treg) activation is crucial for maintaining self-tolerance, but the translational regulation of this process is still poorly understood. Although ribosome biogenesis is considered a housekeeping process, emerging evidence supports the hypothesis that ribosome biogenesis can selectively regulate protein synthesis by tuning translation. Here, we focused on the ribosome biogenesis factor Noc4L, based on the observations that Noc4L is highly expressed in activated Tregs. Conditional Noc4L knockout in Tregs resulted in a lethal autoimmune phenotype resembling Treg-deficient scurfy mice. Interestingly, the Noc4L defect did not globally affect overall protein translation in Tregs but was selectively detrimental to the expression of mRNAs related to Treg activation. These results demonstrate the critical role of Noc4L-mediated ribosome biogenesis in controlling the activation of Tregs and maintaining immune tolerance.