GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335307/suppl/filelist.txtftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335307/suppl/GSE335307_aggregation.csv.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335307/suppl/GSE335307_RAW.tarftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335307/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335307GEOGSEfalseEffect of keratinocyte-intrinsic VISTA deletion on UV-induced type I interferon and inflammatory gene expression in mouse epidermis [scRNA-seq]Type I interferon (IFN-I) signaling is a central driver of cutaneous lupus erythematosus (CLE), but the keratinocyte-intrinsic checkpoints that restrain UV-triggered IFN-I responses remain poorly defined. Here we report that the immune checkpoint VISTA (encoded by Vsir) is expressed in epidermal keratinocytes and acts cell-intrinsically to suppress cGAS–STING–dependent IFN-I induction following ultraviolet (UV) exposure. Conditional deletion of Vsir in keratinocytes (K14Cre-Vsir^fl/fl^) results in markedly elevated expression of interferon-stimulated genes (ISGs), chemokines, and antigen presentation machinery at baseline and is further amplified by acute UVB irradiation. Co-deletion of STING (Sting1) abrogates this hyperinflammatory transcriptional program, placing VISTA upstream of the cGAS–STING–IFN-I axis. Mechanistically, our data support a model in which VISTA restrains EGFR/LRIG1/NUMB-dependent stabilization of phosphorylated (pY245) STING, thereby tuning the magnitude of UV-induced IFN-I output. These findings identify a keratinocyte-intrinsic role for VISTA in suppressing sterile cutaneous inflammation and have translational relevance for photosensitive autoimmune skin disease and for cutaneous immune-related adverse events of VISTA-targeted therapies.2026/06/16GSE335307GSM981000330172335307Mus musculus