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

K. E. Nograles, L. C. Zaba, E. Guttman-Yassky, J. Fuentes-Duculan, M. Suárez-Fariñas, I. Cardinale, A. Khatcherian, J. Gonzalez, K. C. Pierson, T. R. White, C. Pensabene, I. Coats, I. Novitskaya, M. A. Lowes, J. G. Krueger

Research output: Contribution to journalArticle

526 Scopus citations

Abstract

Background: Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines, yet the relative contribution of interferon (IFN)-γ, 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-γ, 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-γ, 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.

Original languageEnglish (US)
Pages (from-to)1092-1102
Number of pages11
JournalBritish Journal of Dermatology
Volume159
Issue number5
DOIs
StatePublished - Nov 1 2008

Keywords

  • Interleukin-17
  • Interleukin-22
  • Keratinocytes
  • Th1
  • Th17

ASJC Scopus subject areas

  • Dermatology

Fingerprint Dive into the research topics of 'Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways'. Together they form a unique fingerprint.

  • Cite this

    Nograles, K. E., Zaba, L. C., Guttman-Yassky, E., Fuentes-Duculan, J., Suárez-Fariñas, M., Cardinale, I., Khatcherian, A., Gonzalez, J., Pierson, K. C., White, T. R., Pensabene, C., Coats, I., Novitskaya, I., Lowes, M. A., & Krueger, J. G. (2008). Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. British Journal of Dermatology, 159(5), 1092-1102. https://doi.org/10.1111/j.1365-2133.2008.08769.x