| First Author | Moore MJ | Year | 2018 |
| Journal | Elife | Volume | 7 |
| PubMed ID | 29848443 | Mgi Jnum | J:316373 |
| Mgi Id | MGI:6834404 | Doi | 10.7554/eLife.33057 |
| Citation | Moore MJ, et al. (2018) ZFP36 RNA-binding proteins restrain T cell activation and anti-viral immunity. Elife 7:e33057 |
| abstractText | Dynamic post-transcriptional control of RNA expression by RNA-binding proteins (RBPs) is critical during immune response. ZFP36 RBPs are prominent inflammatory regulators linked to autoimmunity and cancer, but functions in adaptive immunity are less clear. We used HITS-CLIP to define ZFP36 targets in mouse T cells, revealing unanticipated actions in regulating T-cell activation, proliferation, and effector functions. Transcriptome and ribosome profiling showed that ZFP36 represses mRNA target abundance and translation, notably through novel AU-rich sites in coding sequence. Functional studies revealed that ZFP36 regulates early T-cell activation kinetics cell autonomously, by attenuating activation marker expression, limiting T cell expansion, and promoting apoptosis. Strikingly, loss of ZFP36 in vivo accelerated T cell responses to acute viral infection and enhanced anti-viral immunity. These findings uncover a critical role for ZFP36 RBPs in restraining T cell expansion and effector functions, and suggest ZFP36 inhibition as a strategy to enhance immune-based therapies. |
