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J Allergy Clin Immunol. 2009 Sep;124(3):485-93, 493.e1. doi: 10.1016/j.jaci.2009.05.042. Epub 2009 Aug 8.

Filaggrin-deficient mice exhibit TH17-dominated skin inflammation and permissiveness to epicutaneous sensitization with protein antigen.

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  • 1Division of Immunology, Department of Pediatrics, Harvard Medical School, Children's Hospital, Boston, Mass 02115, USA.

Abstract

BACKGROUND:

Filaggrin is important for skin barrier function and is mutated in 15% to 20% of patients with atopic dermatitis.

OBJECTIVE:

To examine whether filaggrin deficiency predisposes to skin inflammation and epicutaneous sensitization with protein antigen.

METHODS:

Skin histology in filaggrin-deficient flaky tail (ft)/ft mice and wild-type controls was assessed by Hematoxylin and Eosin (H&E) staining and immunohistochemistry. Cytokine mRNA expression was examined by quantitative RT-PCR. Serum antibody levels and splenocyte secretion of cytokines were measured by ELISA.

RESULTS:

The ft/ft mice developed eczematous skin lesions after age 28 weeks and a progressive increase in serum IgE and IgG(1) levels. Normal-appearing skin from 8-week-old ft/ft mice had epidermal thickening and increased dermal infiltration with CD4(+) cells and expression of mRNA for IL-17, IL-6, and IL-23, but not IL-4, IL-13, or IFN-gamma. Lesional skin of 32-week-old ft/ft mice exhibited qualitatively similar, but more pronounced, changes, and elevated IL-4 mRNA levels. Epicutaneous application of ovalbumin to shaved skin of 8-week-old ft/ft mice, but not WT mice, resulted in increased epidermal thickening, dermal infiltration by CD4(+) cells but not eosinophils, and expression of IL-17, IL-6, IL-23, IL-4, and IFN-gamma, but not IL-5 or IL-13, mRNA. Splenocytes from epicutaneously sensitized ft/ft mice, but not controls, secreted cytokines in response to ovalbumin stimulation, and their sera, but not those of controls, contained ovalbumin-specific IgE and IgG(1) antibodies.

CONCLUSION:

Filaggrin-deficient mice exhibit T(H)17-dominated skin inflammation and eczematous changes with age, and are permissive to epicutaneous sensitization with protein antigen.

PMID:
19665780
[PubMed - indexed for MEDLINE]
PMCID:
PMC2886150
Free PMC Article
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