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.
from sddb import Catalog
cohort = Catalog().collection("geo-gse333617")
cohort.members # the 4 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse333617")
coll.ordered_artifacts.to_dataframe() # the 4 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse333617 --dest data/Licenses: 4 NCBI GEO policy
No linked publication found — please cite the data source.