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

Publication date: Available online 20 August 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Ana PM. Serezani, Gunseli Bozdogan, Sarita Sehra, Daniel Walsh, Purna Krishnamurthy, Elizabeth A. Sierra Potchanant, Grzegorz Nalepa, Shreevrat Goenka, Matthew J. Turner, Dan F. Spandau, Mark H. Kaplan
BackgroundAtopic 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 interleukin (IL)-4. Yet, still little is known regarding the direct effects of IL-4 on keratinocyte function.Objective and MethodsIn this report, RNA-seq and functional assays were used to define the impact of the allergic environment on primary keratinocyte function and wound repair in mice.ResultsAcute or chronic stimulation by IL-4 modified expression of over 1000 genes expressed in human keratinocytes that are involved in a broad spectrum of non-overlapping functions. Among the IL-4-induced changes, repression of fibronectin critically impaired the human keratinocyte wounding 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 likely important for the clinical manifestations and pathology of allergic skin disease.

Teaser

IL-4 induces changes in gene expression in keratinocytes that result in impaired re-epithelialization of wounds in vitro and in vivo.


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