{Reference Type}: Journal Article
{Title}: Interleukin 22 early affects keratinocyte differentiation, but not proliferation, in a three-dimensional model of normal human skin.
{Author}: Donetti E;Cornaghi L;Arnaboldi F;Landoni F;Romagnoli P;Mastroianni N;Pescitelli L;Baruffaldi Preis FW;Prignano F;
{Journal}: Exp Cell Res
{Volume}: 345
{Issue}: 2
{Year}: 07 2016 15
{Factor}: 4.145
{DOI}: 10.1016/j.yexcr.2016.05.004
{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.