Stevens-Johnson syndrome/toxic epidermal necrolysis mouse model generated by using PBMCs and the skin of patients - 30/01/13
, Naoya Yoshioka, PhD a, , Riichiro Abe, MD, PhD a, ⁎ 
, Hongjiang Qiao, MD, PhD a, Yasuyuki Fujita, MD, PhD a, Daichi Hoshina, MD a, Asuka Suto, DVM a, Satoru Kase, MD, PhD b, Nobuyoshi Kitaichi, MD, PhD b, Michitaka Ozaki, MD, PhD c, Hiroshi Shimizu, MD, PhD a, ⁎ Corresponding authors: Riichiro Abe, MD, PhD, Department of Dermatology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo 060-8638, Japan.Hiroshi Shimizu, MD, PhD, Department of Dermatology, Hokkaido University Graduate School of Medicine, N15 W7, Sapporo 060-8638, Japan.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-2Rγnull (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.
Conclusion |
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.
Le texte complet de cet article est disponible en PDF.Key words : Stevens-Johnson syndrome, toxic epidermal necrolysis, animal models
Abbreviations used : APC, CTL, DC, FITC, GVHD, GVHR, NK, NOG, ODSR, PE, sFasL, SJS, TEN, TUNEL
Plan
| Supported in part by Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare of Japan (Research on Allergic Diseases and Immunology; H21-Meneki-Wakate-009 to R.A.) and by the Akiyama Life Science Foundation (to R.A.). |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 2
P. 434 - février 2013 Retour au numéro
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