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 Spandau, Mark Kaplan

Research output: Contribution to journalArticle

16 Citations (Scopus)

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)
JournalJournal of Allergy and Clinical Immunology
DOIs
StateAccepted/In press - Oct 23 2015

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Keratinocytes
Fibronectins
Interleukin-4
Wound Healing
Atopic Dermatitis
Skin
Re-Epithelialization
RNA Sequence Analysis
Clinical Pathology
Wounds and Injuries
Pruritus
Skin Diseases
Cytokines
Gene Expression
Genes

Keywords

  • Atopic dermatitis
  • Fibronectin
  • IL-4
  • Keratinocyte
  • RNA sequencing
  • Wound healing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Serezani, A. P. M., Bozdogan, G., Sehra, S., Walsh, D., Krishnamurthy, P., Sierra Potchanant, E. A., ... Kaplan, M. (Accepted/In press). IL-4 impairs wound healing potential in the skin by repressing fibronectin expression. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2016.07.012

IL-4 impairs wound healing potential in the skin by repressing fibronectin expression. / Serezani, Ana P M; Bozdogan, Gunseli; Sehra, Sarita; Walsh, Daniel; Krishnamurthy, Purna; Sierra Potchanant, Elizabeth A.; Nalepa, Grzegorz; Goenka, Shreevrat; Turner, Matthew J.; Spandau, Dan; Kaplan, Mark.

In: Journal of Allergy and Clinical Immunology, 23.10.2015.

Research output: Contribution to journalArticle

Serezani, APM, Bozdogan, G, Sehra, S, Walsh, D, Krishnamurthy, P, Sierra Potchanant, EA, Nalepa, G, Goenka, S, Turner, MJ, Spandau, D & Kaplan, M 2015, 'IL-4 impairs wound healing potential in the skin by repressing fibronectin expression', Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2016.07.012
Serezani, Ana P M ; Bozdogan, Gunseli ; Sehra, Sarita ; Walsh, Daniel ; Krishnamurthy, Purna ; Sierra Potchanant, Elizabeth A. ; Nalepa, Grzegorz ; Goenka, Shreevrat ; Turner, Matthew J. ; Spandau, Dan ; Kaplan, Mark. / IL-4 impairs wound healing potential in the skin by repressing fibronectin expression. In: Journal of Allergy and Clinical Immunology. 2015.
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