title: IL-4 impairs wound healing potential in the skin by repressing fibronectin expression.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatrics, H.B. Wells Center for Pediatric Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Ana P M
authors.initials: APM
authors.lastname: Serezani
authors.affiliation: Department of Pediatrics, H.B. Wells Center for Pediatric Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Gunseli
authors.initials: G
authors.lastname: Bozdogan
authors.affiliation: Department of Pediatrics, H.B. Wells Center for Pediatric Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Sarita
authors.initials: S
authors.lastname: Sehra
authors.affiliation: Department of Pediatrics, H.B. Wells Center for Pediatric Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Daniel
authors.initials: D
authors.lastname: Walsh
authors.affiliation: Department of Pediatrics, H.B. Wells Center for Pediatric Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Purna
authors.initials: P
authors.lastname: Krishnamurthy
authors.affiliation: Department of Pediatrics, H.B. Wells Center for Pediatric Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind; Division of Pediatric Hematology-Oncology Bone Marrow Failure Program, Indiana University School of Medicine, Indianapolis, Ind; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sierra Potchanant
authors.affiliation: Department of Pediatrics, H.B. Wells Center for Pediatric Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind; Division of Pediatric Hematology-Oncology Bone Marrow Failure Program, Indiana University School of Medicine, Indianapolis, Ind; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Nalepa
authors.affiliation: Department of Pediatrics, H.B. Wells Center for Pediatric Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Shreevrat
authors.initials: S
authors.lastname: Goenka
authors.affiliation: Department of Dermatology, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Turner
authors.affiliation: Department of Dermatology, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Dan F
authors.initials: DF
authors.lastname: Spandau
authors.affiliation: 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: mkaplan2@iupui.edu.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005353:Fibronectins / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050800:STAT6 Transcription Factor / Q000235:genetics; D012867:Skin / Q000276:immunology; D059467:Transcriptome / Q000187:drug effects; D014945:Wound Healing / Q000235:genetics / Q000276:immunology*
chemical_list: D005353:Fibronectins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4
keywords: IL-4; Keratinocyte; RNA sequencing; atopic dermatitis; fibronectin; wound healing