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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE265768 | GEO | 2025/08/13

REPOSITORIES: GEO

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

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

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