Interleukin 22 early affects keratinocyte differentiation, but not proliferation, in a three-dimensional model of normal human skin

Elena Donetti, Laura Cornaghi, Francesca Arnaboldi, Federica Landoni, Paolo Romagnoli, Nicolino Mastroianni, Leonardo Pescitelli, W. Franz Baruffaldi-Preis, Francesca Prignano

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin (IL)-22 is a pro-inflammatory cytokine driving the progression of the psoriatic lesion with other cytokines, as Tumor Necrosis Factor (TNF)-alpha and IL-17. Our study was aimed at evaluating the early effect of IL-22 alone or in combination with TNF-alpha and IL-17 by immunofluorescence on i) keratinocyte (KC) proliferation, ii) terminal differentiation biomarkers as keratin (K) 10 and 17 expression, iii) intercellular junctions. Transmission electron microscopy (TEM) analysis was performed. A model of human skin culture reproducing a psoriatic microenvironment was used. Plastic surgery explants were obtained from healthy young women (n=7) after informed consent. Fragments were divided before adding IL-22 or a combination of the three cytokines, and harvested 24 (T24), 48 (T48), and 72 (T72) h later. From T24, in IL-22 samples we detected a progressive decrease in K10 immunostaining in the spinous layer paralleled by K17 induction. By TEM, after IL-22 incubation, keratin aggregates were evident in the perinuclear area. Occludin immunostaining was not homogeneously distributed. Conversely, KC proliferation was not inhibited by IL-22 alone, but only by the combination of cytokines. Our results suggest that IL-22 affects keratinocyte terminal differentiation, whereas, in order to induce a proliferation impairment, a more complex psoriatic-like microenvironment is needed.

Original languageEnglish
Pages (from-to)247-254
Number of pages8
JournalExperimental Cell Research
Volume345
Issue number2
DOIs
Publication statusPublished - Jul 15 2016
Externally publishedYes

Keywords

  • Interleukin-17
  • Keratin 10
  • Keratin 17
  • Transmission electron microscopy
  • Tumor necrosis factor alpha

ASJC Scopus subject areas

  • Cell Biology

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