title: NKp46+ cells express granulysin in multiple cutaneous adverse drug reactions.
abstract: BACKGROUND
  The spectrum of cutaneous adverse drug reactions (cADRs) ranges from benign presentations to severe life-threatening forms such as toxic epidermal necrolysis (TEN). In TEN, granulysin has been shown to be the key cytotoxic molecule. Still, little is known about the expression of granulysin in other cADRs. As an important source of granulysin, natural killer (NK) cells are of major interest in cADRs. Recently, NKp46 has been identified as the most selective NK-cell marker. However, the role of NKp46(+) cells in cADRs and their contribution to granulysin expression remain to be elucidated.
  
  
  METHODS
  Immunohistochemical and immunofluorescence staining of tissue sections from multiple cADRs were quantitatively and qualitatively evaluated. Further, in vivo and in vitro drug-stimulation tests were performed.
  
  
  RESULTS
  Granulysin is expressed at different levels in multiple cADRs both by NKp46(+) cells and by CD8(+) T cells. Even in mild forms of cADRs, granulysin can be induced in vivo and in vitro in a drug-specific manner. NKp46(+) cells were found to infiltrate the dermal/epidermal junction particularly in TEN.
  
  
  CONCLUSIONS
  The impressive clinical differences of cADRs may not be uniquely explained by the expression of granulysin. Additional factors such as drug-specific activation and recruitment of NKp46(+) cells to the epidermis may play a role in determining the severity of cADRs. Therefore, unraveling the effects of drugs on NK-cell activation and trafficking may help to better understand the cytotoxic mechanisms behind cADRs.
authors.affiliation: Department of Dermatology, Inselspital, University of Bern, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Schlapbach
authors.forename: A
authors.initials: A
authors.lastname: Zawodniak
authors.forename: N
authors.initials: N
authors.lastname: Irla
authors.forename: J
authors.initials: J
authors.lastname: Adam
authors.forename: R E
authors.initials: RE
authors.lastname: Hunger
authors.forename: D
authors.initials: D
authors.lastname: Yerly
authors.forename: W J
authors.initials: WJ
authors.lastname: Pichler
authors.forename: N
authors.initials: N
authors.lastname: Yawalkar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003875:Drug Eruptions / Q000145:classification* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000378:metabolism; D013262:Stevens-Johnson Syndrome / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1