| First Author | Luca D | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 9 | Pages | eadk0820 |
| PubMed ID | 38427731 | Mgi Jnum | J:347912 |
| Mgi Id | MGI:7609435 | Doi | 10.1126/sciadv.adk0820 |
| Citation | Luca D, et al. (2024) Aberrant RNA sensing in regulatory T cells causes systemic autoimmunity. Sci Adv 10(9):eadk0820 |
| abstractText | Chronic and aberrant nucleic acid sensing causes type I IFN-driven autoimmune diseases, designated type I interferonopathies. We found a significant reduction of regulatory T cells (T(regs)) in patients with type I interferonopathies caused by mutations in ADAR1 or IFIH1 (encoding MDA5). We analyzed the underlying mechanisms using murine models and found that T(reg)-specific deletion of Adar1 caused peripheral T(reg) loss and scurfy-like lethal autoimmune disorders. Similarly, knock-in mice with T(reg)-specific expression of an MDA5 gain-of-function mutant caused apoptosis of peripheral T(regs) and severe autoimmunity. Moreover, the impact of ADAR1 deficiency on T(regs) is multifaceted, involving both MDA5 and PKR sensing. Together, our results highlight the dysregulation of T(reg) homeostasis by intrinsic aberrant RNA sensing as a potential determinant for type I interferonopathies. |
