| First Author | Myers DR | Year | 2019 |
| Journal | Cell Rep | Volume | 27 |
| Issue | 6 | Pages | 1858-1874.e6 |
| PubMed ID | 31067469 | Mgi Jnum | J:281832 |
| Mgi Id | MGI:6380754 | Doi | 10.1016/j.celrep.2019.04.037 |
| Citation | Myers DR, et al. (2019) Active Tonic mTORC1 Signals Shape Baseline Translation in Naive T Cells. Cell Rep 27(6):1858-1874.e6 |
| abstractText | Naive CD4(+) T cells are an example of dynamic cell homeostasis: T cells need to avoid autoreactivity while constantly seeing self-peptides, yet they must be primed to react to foreign antigens during infection. The instructive signals that balance this primed yet quiescent state are unknown. Interactions with self-peptides result in membrane-proximal, tonic signals in resting T cells. Here we reveal selective and robust tonic mTORC1 signals in CD4(+) T cells that influence T cell fate decisions. We find that the Ras exchange factor Rasgrp1 is necessary to generate tonic mTORC1 signals. Genome-wide ribosome profiling of resting, primary CD4(+) T cells uncovers a baseline translational landscape rich in mTOR targets linked to mitochondria, oxidative phosphorylation, and splicing. Aberrantly increased tonic mTORC1 signals from a Rasgrp1(Anaef) allele result in immunopathology with spontaneous appearance of T peripheral helper cells, follicular helper T cells, and anti-nuclear antibodies that are preceded by subtle alterations in the translational landscape. |
