Document Detail


Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling.
MedLine Citation:
PMID:  18830273     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Tao Zheng; Min H Oh; Sun Y Oh; John T Schroeder; Adam B Glick; Zhou Zhu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-10-02
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  129     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-11     Completed Date:  2009-03-11     Revised Date:  2012-06-28    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  742-51     Citation Subset:  IM    
Affiliation:
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. tzheng@jhmi.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
CD4-Positive T-Lymphocytes / metabolism
Dermatitis / genetics*,  metabolism*
Fibrosis / metabolism
Immune System
Inflammation
Interleukin-13 / genetics*,  metabolism
Leukocytes, Mononuclear / metabolism
Mast Cells / metabolism
Mice
Mice, Inbred C57BL
Phenotype
Pruritus / genetics*,  metabolism*
Skin / metabolism*
Transgenes*
Grant Support
ID/Acronym/Agency:
AI55064/AI/NIAID NIH HHS; HL079349-01/HL/NHLBI NIH HHS; R01 HL079349-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-13

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