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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:124

Article

Oyoshi, Michiko K.^1,2  Murphy, George F.^3,4  Geha, Raif S.^1,2 

[1] Childrens Hosp, Div Immunol, Boston, MA 02115 USA

[2] Dept Pediat, Boston, MA USA

[3] Brigham & Womens Hosp, Div Dermatopathol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA

关键词: ft/ft mice;    filaggrin;    atopic dermatitis;    IL-17;    skin;    allergen;   

DOI  :  10.1016/j.jaci.2009.05.042

来源: Elsevier

【 摘 要 】

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 IgG1 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. (J Allergy Clin Immunol 2009;124:485-93.)

【 授权许可】

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