期刊论文详细信息
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 卷:129
IL-31 regulates differentiation and filaggrin expression in human organotypic skin models
Article
Cornelissen, Christian1  Marquardt, Yvonne2  Czaja, Katharina2  Wenzel, Joerg3  Frank, Jorge4,5  Luescher-Firzlaff, Juliane1  Luescher, Bernhard1  Baron, Jens M.2 
[1] Rhein Westfal TH Aachen, Inst Biochem & Mol Biol, D-52074 Aachen, Germany
[2] Rhein Westfal TH Aachen, Dept Dermatol & Allergol, D-52074 Aachen, Germany
[3] Univ Bonn, Dept Dermatol, Bonn, Germany
[4] Univ Dusseldorf, Dept Dermatol, Dusseldorf, Germany
[5] Maastricht Univ, GROW Sch Oncol & Dev Biol, Med Ctr, Maastricht, Netherlands
关键词: Atopic dermatitis;    differentiation;    filaggrin;    HaCaT;    IL-20;    IL-24;    IL-31;    keratinocyte;    organotypic skin model;    proliferation;   
DOI  :  10.1016/j.jaci.2011.10.042
来源: Elsevier
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【 摘 要 】

Background: Atopic dermatitis (AD) is an inflammatory skin disease affecting 10% to 20% of children and 1% to 3% of adults in industrialized countries. Enhanced expression of IL-31 is detected in skin samples of patients with AD, but its physiological relevance is not known. Objective: We sought to determine the role of IL-31 in skin differentiation. Methods: We used human 3-dimensional organotypic skin models with either primary keratinocytes or HaCaT keratinocytes with inducible IL-31 receptor alpha to evaluate the effect of IL-31. The consequences were studied by using histology, the expression of markers analyzed by immunofluoresence and quantitative RT-PCR, and gene expression arrays. Results: We observed that IL-31 interferes with keratinocyte differentiation. Gene expression analysis revealed a limited set of genes deregulated in response to IL-31, including IL20 and IL24. In HaCaT keratinocytes with inducible IL-31 receptor alpha, IL-31 inhibited proliferation upon induction of IL-31 receptor alpha by inducing cell cycle arrest. As in primary cells, IL-31-treated HaCaT cells elicited a differentiation defect in organotypic skin models, associated with reduced epidermal thickness, disturbed epidermal constitution, altered alignment of the stratum basale, and poor development of the stratum granulosum. The differentiation defect was associated with a profound repression of terminal differentiation markers, including filaggrin, an essential factor for skin barrier formation, and a reduced lipid envelope. The highly induced proinflammatory cytokines IL-20 and IL-24 were responsible for part of the effect on FLG expression and thus for terminal differentiation. Conclusion: Our study suggests that IL-31 is an important regulator of keratinocyte differentiation and demonstrates a link between the presence of IL-31 in skin, as found in patients with AD, and filaggrin expression. (J Allergy Clin Immunol 2012;129:426-33.)

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