IL-31 regulates differentiation and filaggrin expression in human organotypic skin models - 03/02/12
⁎ 
, Jens M. Baron, MD b, ⁎ Corresponding author: Bernhard Lüscher, PhD, Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany.Jens M. Baron, MD, Department of Dermatology and Allergology, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany.Abstract |
Background |
Atopic dermatitis (AD) is an inflammatory skin disease affecting 10% to 20% of children and 1% to 3% of adults in industrialized countries. Enhanced expression of IL-31 is detected in skin samples of patients with AD, but its physiological relevance is not known.
Objective |
We sought to determine the role of IL-31 in skin differentiation.
Methods |
We used human 3-dimensional organotypic skin models with either primary keratinocytes or HaCaT keratinocytes with inducible IL-31 receptor ⍺ to evaluate the effect of IL-31. The consequences were studied by using histology, the expression of markers analyzed by immunofluoresence and quantitative RT-PCR, and gene expression arrays.
Results |
We observed that IL-31 interferes with keratinocyte differentiation. Gene expression analysis revealed a limited set of genes deregulated in response to IL-31, including IL20 and IL24. In HaCaT keratinocytes with inducible IL-31 receptor ⍺, IL-31 inhibited proliferation upon induction of IL-31 receptor ⍺ by inducing cell cycle arrest. As in primary cells, IL-31–treated HaCaT cells elicited a differentiation defect in organotypic skin models, associated with reduced epidermal thickness, disturbed epidermal constitution, altered alignment of the stratum basale, and poor development of the stratum granulosum. The differentiation defect was associated with a profound repression of terminal differentiation markers, including filaggrin, an essential factor for skin barrier formation, and a reduced lipid envelope. The highly induced proinflammatory cytokines IL-20 and IL-24 were responsible for part of the effect on FLG expression and thus for terminal differentiation.
Conclusion |
Our study suggests that IL-31 is an important regulator of keratinocyte differentiation and demonstrates a link between the presence of IL-31 in skin, as found in patients with AD, and filaggrin expression.
Le texte complet de cet article est disponible en PDF.Key words : Atopic dermatitis, differentiation, filaggrin, HaCaT, IL-20, IL-24, IL-31, keratinocyte, organotypic skin model, proliferation
Abbreviations used : 3D, AD, IL-31RA, JAK, MCs, NHEKs, OSMRβ, PI3K, STAT
Plan
| This work was supported by the Deutsche Forschungsgemeinschaft Grant SFB 542, project C11, to J.B. and B.L. |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 2
P. 426 - février 2012 Retour au numéro
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