title: Interleukin 22 early affects keratinocyte differentiation, but not proliferation, in a three-dimensional model of normal human skin.
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.
authors.affiliation: Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy. Electronic address: elena.donetti@unimi.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Donetti
authors.affiliation: Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cornaghi
authors.affiliation: Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Arnaboldi
authors.affiliation: Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Landoni
authors.affiliation: Department of Experimental and Clinical Medicine, Università degli Studi di Firenze, 50125 Florence, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Romagnoli
authors.affiliation: Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy.
authors.forename: Nicolino
authors.initials: N
authors.lastname: Mastroianni
authors.affiliation: Department of Surgery and Translational Medicine, Università degli Studi di Firenze, 50125 Florence, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pescitelli
authors.affiliation: I.R.C.C.S. Istituto Ortopedico Galeazzi, 20161 Milan, Italy.
authors.forename: Franz W
authors.initials: FW
authors.lastname: Baruffaldi Preis
authors.affiliation: Department of Surgery and Translational Medicine, Università degli Studi di Firenze, 50125 Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Prignano
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007378:Interleukins / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D008954:Models, Biological; D012867:Skin / Q000166:cytology*; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D015415:Biomarkers; D007378:Interleukins; D000097043:Interleukin-22
keywords: Interleukin-17; Keratin 10; Keratin 17; Transmission electron microscopy; Tumor necrosis factor alpha