Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling.
IL-13 has been implicated in the pathogenesis of allergic diseases, including atopic dermatitis (AD). However, a direct role of IL-13 in AD has not been established. We aimed to develop an inducible transgenic model in which IL-13 can be expressed in the skin and to define the resulting dermal phenotype and mechanisms involved. The keratin 5 promoter was used with a tetracycline-inducible system to target IL-13 to the skin. The clinical manifestations, dermal histology, cytokine gene regulation, and systemic immune responses in the transgenic mice were assessed. IL-13 was produced exclusively in the skin and caused a chronic inflammatory phenotype characterized by xerosis and pruritic eczematous lesions; dermal infiltration of CD4+ T cells, mast cells, eosinophils, macrophages, and Langerhans cells; upregulation of chemokine and cytokine genes, including thymic stromal lymphopoietin; and skin remodeling with fibrosis and increased vasculature. The dermal phenotype was accompanied by elevated serum total IgE and IgG1 and increased production of IL-4 and IL-13 by CD4+ cells from lymphoid tissues and peripheral blood mononuclear cells. IL-13 is a potent stimulator of dermal inflammation and remodeling and this transgenic model of AD is a good tool for investigating the underlying mechanisms in the pathogenesis of AD.
Zheng
Tao
T
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. tzheng@jhmi.edu
Oh
Min H
MH
Oh
Sun Y
SY
Schroeder
John T
JT
Glick
Adam B
AB
Zhu
Zhou
Z
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003872:Dermatitis / Q000235:genetics* / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism; D007107:Immune System; D007249:Inflammation; D018793:Interleukin-13 / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011537:Pruritus / Q000235:genetics* / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D019076:Transgenes
D018793:Interleukin-13