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

Ana P.M. 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

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)142-151.e5
JournalJournal of Allergy and Clinical Immunology
Volume139
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • IL-4
  • Keratinocyte
  • RNA sequencing
  • atopic dermatitis
  • fibronectin
  • wound healing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Serezani, A. P. M., Bozdogan, G., Sehra, S., Walsh, D., Krishnamurthy, P., Sierra Potchanant, E. A., Nalepa, G., Goenka, S., Turner, M. J., Spandau, D. F., & Kaplan, M. H. (2017). IL-4 impairs wound healing potential in the skin by repressing fibronectin expression. Journal of Allergy and Clinical Immunology, 139(1), 142-151.e5. https://doi.org/10.1016/j.jaci.2016.07.012