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

J Allergy Clin Immunol

Department of Pediatrics, H.B. Wells Center for Pediatric Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind. Electronic address:

Published: January 2017

Background: 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 Methods: In 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.

Results: Acute 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.

Conclusion: Keratinocyte 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222746PMC
http://dx.doi.org/10.1016/j.jaci.2016.07.012DOI Listing

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