Human Gene Set: CHUNG_BLISTER_CYTOTOXICITY_DN


Standard name CHUNG_BLISTER_CYTOTOXICITY_DN
Systematic name M10850
Brief description Genes down-regulated in blister cells from patients with adverse drug reactions (ADR).
Full description or abstract 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 19029983   Authors: Chung WH,Hung SI,Yang JY,Su SC,Huang SP,Wei CY,Chin SW,Chiou CC,Chu SC,Ho HC,Yang CH,Lu CF,Wu JY,Liao YD,Chen YT
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.0: First introduced

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