Atopic dermatitis and skin diseaseFilaggrin-deficient mice exhibit TH17-dominated skin inflammation and permissiveness to epicutaneous sensitization with protein antigen
Section snippets
Mice
Flaky tail mice were purchased from Jackson Laboratory (Bar Harbor, Maine). C57BL6 and BALB/c wild-type (WT) mice were from Charles River Laboratories (Wilmington, Mass). All mice were bred in our animal facility, kept in a specific pathogen-free environment, and fed an ovalbumin-free diet. All procedures performed on the mice were in accordance with the Animal Care and Use Committee of the Children's Hospital Boston.
Epicutaneous sensitization and intraperitoneal immunization
The skin of anesthetized 8-week-old female mice was shaved. Then 100 μg
The ft/ft mice develop eczematous skin lesions
Neonatal ft/ft mice appear normal at birth but have increased TEWL.18 The flaky tail phenotype appears at about 3 days of age with the skin having a dry, scaly appearance.15 There is gradual improvement of the skin condition, and 3-week-old ft/ft pups appear normal, except for shortened ears and loss of tail tips in some mice. Because ft/ft mice are not on a homogenous C57BL6 background, we used both C57BL6 and BALB/c mice as controls. These 2 strains lie on opposite ends of the spectrum of TH
Discussion
We demonstrate that filaggrin deficiency is associated with TH17-dominated skin inflammation, development of eczematous skin lesions with age, and permissiveness to epicutaneous sensitization with protein antigen.
Except for matted hair, there were no discernible skin lesions in ft/ft mice until about 28 weeks of age. By 32 weeks of age, ft/ft mice developed scaly eczematous skin lesions (Fig 1, A). Skin lesions have not been previously described in ft/ft mice,18 possibly because previous
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Supported by the Atopic Dermatitis and Vaccinia Immunization Network, contract NO1 AI 40030, and USPHS grant AR-047417.
Disclosure of potential conflict of interest: G. F. Murphy has received research support from the National Institutes of Health. The rest of the authors have declared that they have no conflict of interest.