Aberrant RNA sensing in regulatory T cells causes systemic autoimmunity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38427731.
- Also identified by DOI 10.1126/sciadv.adk0820 and PMC identifier 10906915.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sub>regs</sub>) in patients with type I interferonopathies caused by mutations in <i>ADAR1</i> or <i>IFIH1</i> (encoding MDA5). We analyzed the underlying mechanisms using murine models and found that T<sub>reg</sub>-specific deletion of <i>Adar1</i> caused peripheral T<sub>reg</sub> loss and <i>scurfy</i>-like lethal autoimmune disorders. Similarly, knock-in mice with T<sub>reg</sub>-specific expression of an MDA5 gain-of-function mutant caused apoptosis of peripheral T<sub>regs</sub> and severe autoimmunity. Moreover, the impact of ADAR1 deficiency on T<sub>regs</sub> is multifaceted, involving both MDA5 and PKR sensing. Together, our results highlight the dysregulation of T<sub>reg</sub> homeostasis by intrinsic aberrant RNA sensing as a potential determinant for type I interferonopathies.
Medical subject headings
- Autoimmune Diseases
- Nucleic Acids