| First Author | Wang WL | Year | 2022 |
| Journal | PLoS Biol | Volume | 20 |
| Issue | 2 | Pages | e3001552 |
| PubMed ID | 35180231 | Mgi Jnum | J:330308 |
| Mgi Id | MGI:6887059 | Doi | 10.1371/journal.pbio.3001552 |
| Citation | Wang WL, et al. (2022) microRNA-142 guards against autoimmunity by controlling Treg cell homeostasis and function. PLoS Biol 20(2):e3001552 |
| abstractText | Regulatory T (Treg) cells are critical in preventing aberrant immune responses. Posttranscriptional control of gene expression by microRNA (miRNA) has recently emerged as an essential genetic element for Treg cell function. Here, we report that mice with Treg cell-specific ablation of miR-142 (hereafter Foxp3CremiR-142fl/fl mice) developed a fatal systemic autoimmune disorder due to a breakdown in peripheral T-cell tolerance. Foxp3CremiR-142fl/fl mice displayed a significant decrease in the abundance and suppressive capacity of Treg cells. Expression profiling of miR-142-deficient Treg cells revealed an up-regulation of multiple genes in the interferon gamma (IFNgamma) signaling network. We identified several of these IFNgamma-associated genes as direct miR-142-3p targets and observed excessive IFNgamma production and signaling in miR-142-deficient Treg cells. Ifng ablation rescued the Treg cell homeostatic defect and alleviated development of autoimmunity in Foxp3CremiR-142fl/fl mice. Thus, our findings implicate miR-142 as an indispensable regulator of Treg cell homeostasis that exerts its function by attenuating IFNgamma responses. |
