IL-4 impairs wound healing potential in the skin by repressing fibronectin expression

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• 作者：Ana P.M. Serezani ; PhD^a ; Gunseli Bozdogan ; MD^a ; Sarita Sehra ; PhD^a ; Daniel Walsh ; BS^a ; Purna Krishnamurthy ; MS^a ; Elizabeth A. Sierra Potchanant ; PhD^a ; ^b ; ^c ; Grzegorz Nalepa ; MD ; PhD^a ; ^b ; ^c ; Shreevrat Goenka ; PhD^a ; Matthew J. Turner ; MD ; PhD^d ; Dan F. Spandau ; PhD^d ; Mark H. Kaplan ; PhD^a ; ^{mkaplan2@iupui.edu}
• 关键词：Keratinocyte ; atopic dermatitis ; wound healing ; IL-4 ; RNA sequencing ; fibronectin
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：139
• 期：1
• 页码：142-151.e5
• 全文大小：5548 K
• 卷排序：139

文摘

Atopic dermatitis (AD) is characterized by intense pruritis and is a common childhood inflammatory disease. Many factors are known to affect AD development, including the pleiotropic cytokine IL-4. Yet little is known regarding the direct effects of IL-4 on keratinocyte function.Objective and MethodsIn this report RNA sequencing and functional assays were used to define the effect of the allergic environment on primary keratinocyte function and wound repair in mice.ResultsAcute or chronic stimulation by IL-4 modified expression of more than 1000 genes expressed in human keratinocytes that are involved in a broad spectrum of nonoverlapping functions. Among the IL-4–induced changes, repression of fibronectin critically impaired the human keratinocyte wound response. Moreover, in mouse models of spontaneous and induced AD-like lesions, there was delayed re-epithelialization. Importantly, topical treatment with fibronectin restored the epidermal repair response.ConclusionKeratinocyte gene expression is critically shaped by IL-4, altering cell fate decisions, which are likely important for the clinical manifestations and pathology of allergic skin disease.