IL-19 is a component of the pathogenetic IL-23/IL-17 cascade in psoriasis

J Invest Dermatol. 2014 Nov;134(11):2757-2767. doi: 10.1038/jid.2014.308. Epub 2014 Jul 21.

Abstract

Psoriasis is a common chronic inflammatory disease with characteristic skin alterations and functions as a model of immune-mediated disorders. Cytokines have a key role in psoriasis pathogenesis. Here, we demonstrated that out of 30 individually quantified cytokines, IL-19 showed the strongest differential expression between psoriatic lesions and healthy skin. Cutaneous IL-19 overproduction was reflected by elevated IL-19 blood levels that correlated with psoriasis severity. Accordingly, anti-psoriatic therapies substantially reduced both cutaneous and systemic IL-19 levels. IL-19 production was induced in keratinocytes by IL-17A and was further amplified by tumor necrosis factor-α and IL-22. Among skin cells, keratinocytes were found to be important targets of IL-19. IL-19 alone, however, regulated only a few keratinocyte functions. While increasing the production of S100A7/8/9 and, to a moderate extent, also IL-1β, IL-20, chemokine C-X-C motif ligand 8, and matrix metalloproteinase 1, IL-19 had no clear influence on the differentiation, proliferation, or migration of these cells. Importantly, IL-19 amplified many IL-17A effects on keratinocytes, including the induction of β-defensins, IL-19, IL-23p19, and T helper type 17-cell- and neutrophil-attracting chemokines. In summary, IL-19 as a component of the IL-23/IL-17 axis strengthens the IL-17A action and might be a biomarker for the activity of this axis in chronic inflammatory disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Gene Expression Regulation*
  • Humans
  • Inflammation
  • Interleukin-17 / metabolism*
  • Interleukin-23 / metabolism*
  • Interleukins / metabolism*
  • Keratinocytes / cytology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Psoriasis / metabolism*
  • Skin / immunology
  • Skin / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • IL19 protein, human
  • Interleukin-17
  • Interleukin-23
  • Interleukins
  • Tumor Necrosis Factor-alpha