Serezani, Ana PMBozdogan, GunseliSehra, SaritaWalsh, DanielKrishnamurthy, PurnaPotchanant, Elizabeth A SierraNalepa, GrzegorzGoenka, ShreevratTurner, Matthew J.Spandau, Dan F.Kaplan, Mark H.2018-05-252018-05-252017-01Serezani, A. P., Bozdogan, G., Sehra, S., Walsh, D., Krishnamurthy, P., Potchanant, E. A. S., … Kaplan, M. H. (2017). IL-4 impairs wound healing potential in the skin by repressing fibronectin expression. The Journal of Allergy and Clinical Immunology, 139(1), 142–151.e5. http://doi.org/10.1016/j.jaci.2016.07.012https://hdl.handle.net/1805/16255BACKGROUND: 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.en-USPublisher PolicyIL-4KeratinocyteRNA sequencingAtopic dermatitisFibronectinWound healingArticle