The ubiquitin E3 ligase TRIM21 suppresses type I interferon signaling via STING degradation and ameliorates systemic autoimmunity.

ABSTRACT: Tripartite motif-containing 21 (TRIM21) is a cytoplasmic protein with E3 ubiquitin ligase activity. Although autoantibodies against TRIM21 are frequently detected in patients with systemic lupus erythematosus (SLE), its role in disease pathogenesis remains unclear. Here we demonstrate that TRIM21 directly interacts with the stimulator of interferon genes (STING) to regulate type I interferon (IFN) production. In both induced and spontaneous murine models of lupus, TRIM21 deficiency exacerbated lupus-like pathology and heightened IFN production after STING activation. By contrast, TRIM21 overexpression attenuated autoimmunity in lupus-prone mice. Mechanistically, TRIM21 binds to STING and promotes its degradation via the ubiquitin-proteasome pathway. In patients with SLE, TRIM21 expression

SUBMITTER: Kim DS 

PROVIDER: S-EPMC12322227 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature