Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson syndrome and toxic epidermal necrolysis.

ABSTRACT: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is a rare but life-threatening cutaneous drug reaction mediated by human leukocyte antigen (HLA) class I-restricted CD8⁺ T cells. For unbiased assessment of cellular immunopathogenesis, here we perform single-cell (sc) transcriptome, surface proteome, and T cell receptor (TCR) sequencing on unaffected skin, affected skin, and blister fluid from 15 SJS/TEN patients. From 109,888 cells, we identify 15 scRNA-defined subsets. Keratinocytes express markers indicating HLA class I-restricted antigen presentation and appear to trigger the proliferation of and killing by cytotoxic CD8⁺ tissue-resident T cells that express granulysin, granzyme B, perforin, LAG3, CD27, and LINC01871, and signal through the PKM, MI

SUBMITTER: Gibson A 

PROVIDER: S-EPMC11461852 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature