Mechanisms of allergy and clinical immunologyDefective natural killer cell activity in a mouse model of eczema herpeticum
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Section snippets
HSV1 strains
The KOS strain of HSV116 and the green fluorescent protein–expressing KOS strain17 were provided by Dr Carl Ware, Sanford-Burnham Medical Research Institute. The McKrae strain (HSV1-McKrae)18, 19 was provided by Dr Homayon Ghiasi, Cedars-Sinai Medical Center, and Dr Feng Yao, Brigham and Women's Hospital.
Mouse model of EH
NC/Nga mice20 were used in all animal experiments. AD-like skin lesions were induced, as described previously.13 Briefly, mice were shaved on the back, and dermatitis was induced by 2 rounds of
Clinical features of a murine EH model
We sought to develop a model of EH in dermatitis-prone NC/Nga mice.20 First, eczema was induced by means of epicutaneous applications of D farinae extract and SEB. Seven days after the last D farinae/SEB administration, eczematous and normal (sham-treated) mice were infected with the McKrae strain of HSV1 (HSV1-McKrae)18, 19 on 4 sites of shaved back skin through a combination of scarification and pricking. Skin lesions with bleeding and exudates started to develop on day 2 after infection at
Discussion
Impaired skin barrier function is an underlying factor for AD, as well as increased susceptibility to HSV1 infection. In this study we showed that reduced NK cell activity (not number) plays a critical role in the HSV1-induced development of severe skin lesions in eczematous mice. The role of NK cells in defense against HSV1-induced skin lesions in our EH model is similar to that found in our eczema vaccinatum model.14 NK cell depletion and reconstitution were performed similarly in both eczema
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2019, Life SciencesCitation Excerpt :Thus, ORAI1-deficient patients are highly susceptible to infections such as viral infection [21]. In atopic dermatitis like mice we observed lower NK cell activity and more susceptible to virus [71]. Taken together, we may infer that targeting on ORAI1 may improve NK cell malfunction and reduce the risk of virus infection.
Advances in atopic dermatitis in 2017
2018, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Normal mice not predisposed to skin breakdown exhibited less severe herpes simplex virus 1 lesions with improved NK cell activity compared with eczematous mice. These results suggest that a lack of dysfunctional NK cells might also play a role in the development of more severe skin superinfection in those with eczematous skin.10 Several studies commented on the protective role of normal skin flora to keep S aureus overgrowth in check.
Advances in mechanisms of allergic disease in 2017
2018, Journal of Allergy and Clinical ImmunologyCitation Excerpt :These cells exhibited low proliferative rates in response to cytokines and impaired antitumor activity that can be partially restored by antibody-mediated disruption of PD-1/programmed death ligand interaction.22 In a mouse model of eczema herpeticum with an impaired skin barrier, a critical role of defective NK activities was demonstrated for the development of herpes simplex virus 1–induced severe skin lesions.23 Increased numbers of MCs at sites of inflammation might be a driving mechanism, a bystander effect, or a host-driven compensatory mechanism to control and terminate disease.
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2023, Clinical and Experimental Vaccine Research
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.
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.
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Dr Lee is currently affiliated with the Department of Dermatology, Gil Medical Center, Gachon University, Incheon City, Republic of Korea.
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Dr Choi is currently affiliated with the Department of Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea.