Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 139, Issue 1, Pages 142-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2016.07.012
Keywords
Keratinocyte; atopic dermatitis; wound healing; IL-4; RNA sequencing; fibronectin
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Funding
- Public Health Service grant [R01 AI095282, R01 ES020866]
- NIH K12-Indiana Pediatric Scientist Award [5T32H0069047-04]
- VA [CDA2 CX001019]
- Riley Children's Foundation
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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.
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