Noc4L Dependent Ribosome Biogenesis Controls Treg Activation

Abstract

Tregs 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 a new hypothesis that different types of cells may actually contain distinct repertoires of ribosome biogenesis factors that generate specialized ribosomes and confer the translation of selected mRNAs. Here, we focused on the ribosome biogenesis factor Noc4L, based on the observations that Noc4L is highly expressed in activated Treg cells. Conditional Noc4L knockout in Tregs resulted in a lethal autoimmune phenotype, resembling Treg deficient scurfy mice. Interestingly, the Noc4L defect did not globally affect the overall protein translation in Tregs but rather was selectively detrimental to the expression of genes related to Treg activation. These results demonstrate the critical role of Noc4L dependent ribosome biogenesis in controlling the activation of Tregs and maintaining immune tolerance.