IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes

K Boniface, FX Bernard, M Garcia… - The Journal of …, 2005 - journals.aai.org
K Boniface, FX Bernard, M Garcia, AL Gurney, JC Lecron, F Morel
The Journal of Immunology, 2005journals.aai.org
IL-22 belongs to a family of cytokines structurally related to IL-10, including IL-19, IL-20, IL-
24, and IL-26. In contrast to IL-10, IL-22 has proinflammatory activities. IL-22 signals through
a class II cytokine receptor composed of an IL-22-binding chain, IL-22RA1, and the IL-10RB
subunit, which is shared with the IL-10R. In the present study, we show that short-term
cultured human epidermal keratinocytes express a functional IL-22R but no IL-10R.
Accordingly, IL-22 but not IL-10 induces STAT3 activation in keratinocytes. Using a cDNA …
Abstract
IL-22 belongs to a family of cytokines structurally related to IL-10, including IL-19, IL-20, IL-24, and IL-26. In contrast to IL-10, IL-22 has proinflammatory activities. IL-22 signals through a class II cytokine receptor composed of an IL-22-binding chain, IL-22RA1, and the IL-10RB subunit, which is shared with the IL-10R. In the present study, we show that short-term cultured human epidermal keratinocytes express a functional IL-22R but no IL-10R. Accordingly, IL-22 but not IL-10 induces STAT3 activation in keratinocytes. Using a cDNA array screening approach, real-time RT-PCR, and Western blot analysis, we demonstrate that IL-22 up-regulates, in a dose-dependent manner, the expression of S100A7, S100A8, S100A9, a group of proinflammatory molecules belonging to the S100 family of calcium-binding proteins, as well as the matrix metalloproteinase 3, the platelet-derived growth factor A, and the CXCL5 chemokine. In addition, IL-22 induces keratinocyte migration in an in vitro injury model and down-regulates the expression of at least seven genes associated with keratinocyte differentiation. Finally, we show that IL-22 strongly induces hyperplasia of reconstituted human epidermis. Taken together, these results suggest that IL-22 plays an important role in skin inflammatory processes and wound healing.
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