Defective natural killer cell activity in a mouse model of eczema herpeticum - 19/04/17
Abstract |
Background |
Patients with atopic dermatitis (AD) are susceptible to several viruses, including herpes simplex virus (HSV). Some patients experience 1 or more episodes of a severe skin infection caused by HSV termed eczema herpeticum (EH). There are numerous mouse models of AD, but no established model exists for EH.
Objective |
We sought to establish and characterize a mouse model of EH.
Methods |
We infected AD-like skin lesions with HSV1 to induce severe skin lesions in a dermatitis-prone mouse strain of NC/Nga. Gene expression was investigated by using a microarray and quantitative PCR; antibody titers were measured by means of ELISA; and natural killer (NK) cell, cytotoxic T-cell, regulatory T-cell, and follicular helper T-cell populations were evaluated by using flow cytometry. The role of NK cells in HSV1-induced development of severe skin lesions was examined by means of depletion and adoptive transfer.
Results |
Inoculation of HSV1 induced severe erosive skin lesions in eczematous mice, which had an impaired skin barrier, but milder lesions in small numbers of normal mice. Eczematous mice exhibited lower NK cell activity but similar cytotoxic T-cell activity and humoral immune responses compared with normal mice. The role of NK cells in controlling HSV1-induced skin lesions was demonstrated by experiments depleting or transferring NK cells.
Conclusion |
A murine model of EH with an impaired skin barrier was established in this study. We demonstrated a critical role of defective NK activities in the development of HSV1-induced severe skin lesions in eczematous mice.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Atopic dermatitis, eczema herpeticum, herpes simplex virus, animal model, natural killer cell
Abbreviations used : AD, EC-OVA model, EH, Foxp3, HSV, NK, qPCR, SEB, TEWL, TFH, Treg
Plan
| This study was conducted as part of the Atopic Dermatitis Research Network funded by the National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIH; HHSN272201000020C). T.K. is also supported by NIH grants 5R01AR064418, 5R01HL124283, and 1R21AI115534. |
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| Disclosure of potential conflict of interest: K. Matsumoto is employed by National Research Institute for Child Health and Development, has received payment for lectures from Merck Sharp and Dohme (MSD), Ono Pharmaceutical, GlaxoSmithKline, Kyorin Pharmaceutical, Ohtsuka Pharmaceutical, Mitsubishi Tanabe Pharma, AstraZeneca, Siemens Healthcare, Maruho, and Teijin Pharma. T. Kawakami has received grants from the National Institute of Allergy and Infectious Diseases (HHSN272201000020C and 1R21AI115534); the National Heart, Lung, and Blood Institute (5R01HL124283); the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5R01AR064418)l and the Nipponham Foundation for the Future of Food. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 3
P. 997 - mars 2017 Retour au numéro
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