{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333617/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":[" Other","Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333617"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Targeting JAK1/3-STAT1 signaling attenuates cytotoxic T lymphocytes activation for the treatment in Stevens-Johnson syndrome and toxic epidermal necrolysis","description":"Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs). We integrate single-cell and spatial transcriptomic analyses on blood, blisters, and lesional skin from SJS/TEN patients, revealing IFN-γ and JAK/STAT signaling as the key pathways responsible for driving epidermal necrolysis. We identify JAK1/3–STAT1 signaling as a primary driver of the activation of CD8+ cytotoxic T lymphocytes (CTLs), natural killer (NK)/NKT cells, macrophages and conventional dendritic cells in skin lesions. The high proportion of cytotoxic protein (granulysin and granzyme B)–expressing CD8+ CTLs in SJS/TEN blisters is associated with STAT1 phosphorylation. Immunostaining and ex vivo blocking assays further confirm the potential for the JAK1/3 inhibitor to attenuate CD8+ CTL activation in SJS/TEN. We conduct a proof-of-concept clinical trial in 20 patients with SJS/TEN (ClinicalTrials.gov: NCT06474078), and find that the JAK1/3 inhibitor tofacitinib improves clinical outcomes by reducing skin-healing time with no observed mortality. Our study provides an effective and alternative mechanism-based therapeutic approach for SJS/TEN.","dates":{"publication":"2026/06/25"},"accession":"GSE333617","cross_references":{"GSM":["GSM9769903","GSM9769904","GSM9769901","GSM9769902","GSM9769907","GSM9769908","GSM9769905","GSM9769906","GSM9769921","GSM9769900","GSM9769922","GSM9769920","GSM9769914","GSM9769915","GSM9769912","GSM9769913","GSM9769918","GSM9769919","GSM9769916","GSM9769917","GSM9769910","GSM9769899","GSM9769911","GSM9769897","GSM9769898","GSM9769909"],"GPL":["24676"],"GSE":["333617"],"taxon":["Homo sapiens"]}}