IL-4 impairs wound healing potential in the skin by repressing fibronectin expression - 18/04/17
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.
Le texte complet de cet article est disponible en PDF.Key words : Keratinocyte, atopic dermatitis, wound healing, IL-4, RNA sequencing, fibronectin
Abbreviations used : AD, FLG, FN1, HK, IL-4R, IVL, LOR, RNA-Seq, STAT6, WT
Plan
| Supported by Public Health Service grants R01 AI095282 (to M.H.K.), R01 ES020866 (to D.F.S.), VA CDA2 CX001019 (to M.J.T.), NIH K12–Indiana Pediatric Scientist Award, and T32 (5T32H0069047-04; to G.N.). Support provided by the HB Wells Center was in part from the Riley Children's Foundation. |
|
| Disclosure of potential conflict of interest: G. Nalepa receives grant support from the National Institutes of Health (NIH). M. J. Turner receives grant support from Department of Veterans Affairs (VA career development award CX001019). D. F. Spandau receives grant support from the NIH. M. H. Kaplan receives grant support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 1
P. 142 - janvier 2017 Retour au numéro
Article précédent
- Proton pump inhibitors decrease eotaxin-3/CCL26 expression in patients with chronic rhinosinusitis with nasal polyps: Possible role of the nongastric H,K-ATPase
- Jin-Young Min, Christopher J. Ocampo, Whitney W. Stevens, Caroline P.E. Price, Christopher F. Thompson, Tetsuya Homma, Julia H. Huang, James E. Norton, Lydia A. Suh, Kathryn L. Pothoven, David B. Conley, Kevin C. Welch, Stephanie Shintani-Smith, Anju T. Peters, Leslie C. Grammer, Kathleen E. Harris, Kathryn E. Hulse, Atsushi Kato, Nikolai N. Modyanov, Robert C. Kern, Robert P. Schleimer, Bruce K. Tan
- An IL-17–dominant immune profile is shared across the major orphan forms of ichthyosis
- Amy S. Paller, Yael Renert-Yuval, Maria Suprun, Hitokazu Esaki, Margeaux Oliva, Thy Nhat Huynh, Benjamin Ungar, Norma Kunjravia, Rivka Friedland, Xiangyu Peng, Xiuzhong Zheng, Yeriel D. Estrada, James G. Krueger, Keith A. Choate, Mayte Suárez-Fariñas, Emma Guttman-Yassky
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?