Functional effects of interleukin 31 in human primary keratinocytes


  • Edited by: Thomas Bieber

Sadaf Kasraie, PhD, Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Ricklinger Str. 5, D-30449 Hannover, Germany.
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To cite this article: Kasraie S, Niebuhr M, Baumert K, Werfel T. Functional effects of Interleukin 31 in human primary keratinocytes. Allergy 2011; 66: 845–852.


Background:  Interleukin (IL)-31 is a T-cell cytokine acting through a heterodimeric receptor composed of IL-31RA and OSMR which is expressed on epithelial cells including keratinocytes. A major function of IL-31 in atopic dermatitis (AD) is the induction of pruritus in the skin. Inflammatory effects of IL-31 in human primary keratinocytes (HPKs) still remain unclear. We investigated expression, regulation of the IL-31 receptor as well as functions of IL-31 in HPKs.

Methods:  Human primary keratinocytes were stimulated with TLR-2 ligands (Pam3Cys, lipoteichoic acid and peptidoglycan), or Th1 and Th2 associated cytokines (IFN-γ and IL-4), respectively. IL-31R expression and regulation as well as functional effects of IL-31 stimulation were then investigated at both the mRNA and protein level and compared with HPKs from patients with AD. The STAT signalling pathway and TLR-2 expression were investigated using Western blot and Immunohistochemical stainings, respectively.

Results:  Pam3Cys or IFN-γ significantly up-regulated IL-31RA and OSMR expression. IL-31 activated STAT-3 phosphorylation in HPKs which was augmented after preactivation with Pam3Cys or IFN-γ. IL-31 enhanced the secretion of CCL2 after up-regulation of the receptor with Pam3Cys or IFN-γ. However, this was not observed in keratinocytes from AD patients where an impaired TLR-2 expression was found.

Conclusions:  Together, our findings show a functional role of IL-31 in HPKs and provide a new link between TLR-2 ligands and IL-31 which might be dysregulated in AD. Altered function of IL-31 may have implications for cutaneous inflammation in eczema where skin colonization with Staphylococcus aureus and dysregulation of TLR-2 have been described.