IL-23-mediated psoriasis-like epidermal hyperplasia is dependent on IL-17A

Heather L. Rizzo, Shinji Kagami, Kevin G. Phillips, Stephen E. Kurtz, Steven L. Jacques, Andrew Blauvelt

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140 Scopus citations

Abstract

IL-23 and Th17 cells producing IL-17A and IL-22 are found in excess in skin affected by psoriasis. Previous studies showed that IL-22, but not IL-17A, mediates psoriasis-like epidermal hyperplasia following recombinant murine (rm)IL-23 injections into skin. To further investigate the role of IL-17A, ears of mice were injected with rmIL-23. Investigators blinded to treatment conditions and mouse genotypes measured ear swelling, epidermal thickness, and cytokine expression. In wild-type (WT) mice, rmIL-23 induced ear swelling (p < 0.001, all p values versus saline), epidermal hyperplasia by histology (p < 0.001) and confocal microscopy (p < 0.004), and expression of both IL-17A and IL-22. As expected, rmIL-23 injections into IL-22-/- mice resulted in relatively little ear swelling (p < 0.09) and epidermal hyperplasia (p < 0.51 by histology and p < 0.75 by confocal microscopy). Notably, rmIL-23 injections into IL-17A-/- mice produced little ear swelling (p < 0.001, versus IL-23-injected WT mice) and epidermal hyperplasia (p < 0.001 by histology and p < 0.005 by confocal microscopy), even though IL-22 was readily induced in these mice. Furthermore, systemic delivery of blocking Abs directed against either IL-22 or IL-17A completely inhibited IL-23-induced epidermal hyperplasia in WT mice. These results demonstrate that IL-17A, like IL-22, is a downstream mediator for IL-23-induced changes in murine skin and that both of these Th17 cytokines are necessary to produce IL-23-mediated skin pathology. IL-17A may represent an attractive therapeutic target in individuals with psoriasis by blocking downstream effects of IL-23.

Original languageEnglish (US)
Pages (from-to)1495-1502
Number of pages8
JournalJournal of Immunology
Volume186
Issue number3
DOIs
StatePublished - Feb 1 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Rizzo, H. L., Kagami, S., Phillips, K. G., Kurtz, S. E., Jacques, S. L., & Blauvelt, A. (2011). IL-23-mediated psoriasis-like epidermal hyperplasia is dependent on IL-17A. Journal of Immunology, 186(3), 1495-1502. https://doi.org/10.4049/jimmunol.1001001