| First Author | Sneezum L | Year | 2020 |
| Journal | Front Immunol | Volume | 11 |
| Pages | 1398 | PubMed ID | 32733464 |
| Mgi Jnum | J:336801 | Mgi Id | MGI:6729343 |
| Doi | 10.3389/fimmu.2020.01398 | Citation | Sneezum L, et al. (2020) Context-Dependent IL-1 mRNA-Destabilization by TTP Prevents Dysregulation of Immune Homeostasis Under Steady State Conditions. Front Immunol 11:1398 |
| abstractText | The bioavailability of the major pro-inflammatory cytokines IL-1alpha and IL-1beta is tightly controlled by transcription and post-translational processing to prevent hyperinflammation. The role of mRNA decay in maintenance of physiological IL-1 amounts remained unknown. Here we show that the down-regulation of Il1a and Il1b mRNA by the mRNA-destabilizing protein TTP (gene Zfp36) is required for immune homeostasis. The TTP deficiency syndrome, a multi organ inflammation in TTP (-/-) mice, was significantly ameliorated upon deletion of the IL-1 receptor. Il1a and Il1b played non-redundant roles in triggering the pathological IL-1 signaling in TTP (-/-) mice. Accordingly, tissues from TTP (-/-) animals contained increased amounts of Il1b mRNA. Unexpectedly, TTP destabilized Il1b mRNA in cell type-specific ways as evident from RNA-Seq and mRNA stability assays. These results demonstrate that TTP-driven mRNA destabilization depends on the cellular context. Moreover, such context-defined mRNA decay is essential for keeping steady state IL-1 levels in the physiological range. |
