title: Stevens-Johnson syndrome/toxic epidermal necrolysis mouse model generated by using PBMCs and the skin of patients.
abstract: BACKGROUND
  Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous reactions caused by drugs or infections and exhibiting widespread epidermal necrosis. Currently, there is no animal model that reproduces SJS/TEN symptoms.
  
  
  OBJECTIVE
  We sought to develop a novel mouse model of SJS/TEN by using PBMCs and skin from patients who had recovered from SJS/TEN.
  
  
  METHODS
  For our mouse model, patients' PBMCs were injected intravenously into immunocompromised NOD/Shi-scid, IL-2Rγ(null) (NOG) mice, followed by oral administration of a causative drug. Subsequently, to replace human skin, unaffected skin specimens obtained from patients who had recovered from SJS/TEN were grafted onto NOG mice, after which patient-derived PBMCs and the causative drug were applied.
  
  
  RESULTS
  Mice injected with PBMCs from patients with SJS/TEN and given the causative drug showed marked conjunctival congestion and numerous cell death of conjunctival epithelium, whereas there were no symptoms in mice injected with PBMCs from patients with ordinary drug skin reactions. CD8(+) T lymphocyte-depleted PBMCs from patients with SJS/TEN did not elicit these symptoms. In addition, skin-grafted mice showed darkening of the skin-grafted areas. Cleaved caspase-3 staining showed that dead keratinocytes were more numerous in the skin-grafted mice than in the healthy control animals.
  
  
  CONCLUSIONS
  We have established a novel human-oriented SJS/TEN mouse model and proved the importance of CD8(+) T lymphocytes in SJS/TEN pathogenesis. The mouse model promises to promote diagnostic and therapeutic approaches.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Saito
authors.forename: Naoya
authors.initials: N
authors.lastname: Yoshioka
authors.forename: Riichiro
authors.initials: R
authors.lastname: Abe
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Qiao
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujita
authors.forename: Daichi
authors.initials: D
authors.lastname: Hoshina
authors.forename: Asuka
authors.initials: A
authors.lastname: Suto
authors.forename: Satoru
authors.initials: S
authors.lastname: Kase
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kitaichi
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ozaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD / Q000378:metabolism / Q000502:physiology*; D016513:Mice, SCID / Q000378:metabolism / Q000502:physiology*; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D013262:Stevens-Johnson Syndrome / Q000378:metabolism / Q000473:pathology*
chemical_list: D053148:Caspase 3