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Browsing by Author "Walsh, Daniel"
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Item IL-4 impairs wound healing potential in the skin by repressing fibronectin expression(Elsevier, 2017-01) Serezani, Ana PM; Bozdogan, Gunseli; Sehra, Sarita; Walsh, Daniel; Krishnamurthy, Purna; Potchanant, Elizabeth A Sierra; Nalepa, Grzegorz; Goenka, Shreevrat; Turner, Matthew J.; Spandau, Dan F.; Kaplan, Mark H.; Pediatrics, School of MedicineBACKGROUND: 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.