title: Defective natural killer cell activity in a mouse model of eczema herpeticum.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif; Laboratory for Allergic Disease, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ando
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Jong-Rok
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Gisen
authors.initials: G
authors.lastname: Kim
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Tae
authors.initials: T
authors.lastname: Nakasaki
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Manando
authors.initials: M
authors.lastname: Nakasaki
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Division of Vaccine Development and Center for Infectious Disease, La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
authors.forename: Youn Soo
authors.initials: YS
authors.lastname: Choi
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif; Laboratory for Allergic Disease, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan. Electronic address: toshi@lji.org.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007074:Immunoglobulin G / Q000276:immunology; D007617:Kaposi Varicelliform Eruption / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D018139:Simplexvirus / Q000276:immunology; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G
keywords: Atopic dermatitis; animal model; eczema herpeticum; herpes simplex virus; natural killer cell