Loss of TRIM21 drives UVB-induced systemic inflammation by regulating DNA-sensing pathways

This study investigated the mechanisms underlying photosensitivity in patients with systemic lupus erythematosus (SLE), focusing on the role of type I interferons (IFNs) and TRIM21, an autoantigen in SLE. Through experiments on mice exposed to ultraviolet light B (UVB), we demonstrate that TRIM21 deficiency leads to exacerbated systemic inflammation and IFN-driven responses following UVB exposure, mimicking aspects of SLE pathology. Specifically, we observe enhanced expression of IFN-stimulated genes (ISGs), increased levels of inflammatory chemokines, and elevated IgG deposition in the skin of UVB-exposed Trim21-/- mice. Mechanistic investigations reveal that TRIM21 restrains IFN induction by regulating the STING pathway, impacting the stability of proteins involved in RNA/DNA sensing and IFN responses. These findings shed light on the protective role of TRIM21 against UVB-induced systemic disease in SLE, offering insights into its potential as a therapeutic target to mitigate disease flares and activity in SLE patients. Eight-week-old wild-type (WT) and Trim21-/- mice were shaved dorsally prior to UVB exposure. Mice were allowed to move freely in their cage during UVB exposure and mice were treated with/without UVB 100 mJ/cm2 for one or three weeks. spleens were harvested following final UVB exposure to extract RNA for RNA sequencing