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Br J Dermatol. 2008 Nov;159(5):1092-102. doi: 10.1111/j.1365-2133.2008.08769.x. Epub 2008 Aug 5.

Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways.

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  • 1Laboratory of Investigative Dermatology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.

Abstract

BACKGROUND:

Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines, yet the relative contribution of interferon (IFN)-gamma, interleukin (IL)-17 and IL-22 on disease pathogenesis is still unknown.

OBJECTIVES:

In this study, we sought to identify the cytokines produced by skin-resident T cells in normal skin, localize the receptors for these cytokines, and examine how these cytokines alter gene expression profiles of the cells bearing cognate receptors.

METHODS:

We used intracellular cytokine staining and flow cytometry to evaluate T cell cytokine production, and immunohistochemistry and double-label immunofluorescence to localize cytokine receptors in skin. Gene array analysis of cytokine-treated keratinocytes was performed using moderated paired t-test controlling for false discovery rate using the Benjamini-Hochberg procedure.

RESULTS:

We demonstrate that T-helper cells producing IL-17, IL-22 and/or IFN-gamma, as well as the cells bearing cognate cytokine receptors, are present in normal human skin. Keratinocytes stimulated with IL-17 expressed chemokines that were different from those induced by IFN-gamma, probably contributing to the influx of neutrophils, dendritic cells and memory T cells into the psoriatic lesion. In contrast, IL-22 downregulated genes associated with keratinocyte differentiation and caused epidermal alterations in an organotypic skin model.

CONCLUSIONS:

Our results suggest that the Th17 cytokines IL-17 and IL-22 mediate distinct downstream pathways that contribute to the psoriatic phenotype: IL-17 is more proinflammatory, while IL-22 retards keratinocyte differentiation.

PMID:
18684158
[PubMed - indexed for MEDLINE]
PMCID:
PMC2724264
Free PMC Article

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