Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Published

Journal Article

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening adverse drug reactions characterized by massive epidermal necrosis, in which the specific danger signals involved remain unclear. Here we show that blister cells from skin lesions of SJS-TEN primarily consist of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and both blister fluids and cells were cytotoxic. Gene expression profiling identified granulysin as the most highly expressed cytotoxic molecule, confirmed by quantitative PCR and immunohistochemistry. Granulysin concentrations in the blister fluids were two to four orders of magnitude higher than perforin, granzyme B or soluble Fas ligand concentrations, and depleting granulysin reduced the cytotoxicity. Granulysin in the blister fluids was a 15-kDa secretory form, and injection of it into mouse skin resulted in features mimicking SJS-TEN. Our findings demonstrate that secretory granulysin is a key molecule responsible for the disseminated keratinocyte death in SJS-TEN and highlight a mechanism for CTL- or NK cell--mediated cytotoxicity that does not require direct cellular contact.

Full Text

Duke Authors

Cited Authors

  • Chung, W-H; Hung, S-I; Yang, J-Y; Su, S-C; Huang, S-P; Wei, C-Y; Chin, S-W; Chiou, C-C; Chu, S-C; Ho, H-C; Yang, C-H; Lu, C-F; Wu, J-Y; Liao, Y-D; Chen, Y-T

Published Date

  • December 2008

Published In

Volume / Issue

  • 14 / 12

Start / End Page

  • 1343 - 1350

PubMed ID

  • 19029983

Pubmed Central ID

  • 19029983

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/nm.1884

Language

  • eng

Conference Location

  • United States