title: Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum.
abstract: Threats of bioterrorism have renewed efforts to better understand poxvirus pathogenesis and to develop a safer vaccine against smallpox. Individuals with atopic dermatitis are excluded from smallpox vaccination because of their propensity to develop eczema vaccinatum, a disseminated vaccinia virus (VACV) infection. To study the underlying mechanism of the vulnerability of atopic dermatitis patients to VACV infection, we developed a mouse model of eczema vaccinatum. Virus infection of eczematous skin induced severe primary erosive skin lesions, but not in the skin of healthy mice. Eczematous mice exhibited lower natural killer (NK) cell activity but similar cytotoxic T lymphocyte activity and humoral immune responses. The role of NK cells in controlling VACV-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. The proinflammatory cytokine interleukin (IL)-17 reduced NK cell activity in mice with preexisting dermatitis. Given low NK cell activities and increased IL-17 expression in atopic dermatitis patients, these results can explain the increased susceptibility of atopic dermatitis patients to eczema vaccinatum.
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. yuko@liai.org
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tomimori
authors.forename: Kenji
authors.initials: K
authors.lastname: Yumoto
authors.forename: Shunji
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ando
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tagaya
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology / Q000821:virology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D007617:Kaposi Varicelliform Eruption / Q000276:immunology / Q000473:pathology / Q000821:virology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D051379:Mice; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000821:virology; D012899:Smallpox / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D020381:Interleukin-17