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

GSE265768 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/08/13 Platform GPL24247
Summary
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.
Published in
Loss of Tripartite Motif-Containing Protein 21 and UVB-Induced Systemic Inflammation by Regulating DNA-Sensing Pathways
Tumurkhuu G, Perri G, Moore R et al. · Arthritis & rheumatology (Hoboken, N.J.) 2026 · PMID 40524344 · doi:10.1002/art.43273
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Also filed as BioProject PRJNA1104167 and SRA study SRP503902. Searching any of these in the dataset finder brings you back here.

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