title: The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis.
abstract: Psoriasis is a common chronic skin disease. Recent studies demonstrated that IL-20 and IL-22, cytokines produced by keratinocytes and T cells, respectively, both inhibit keratinocyte terminal differentiation and induce psoriasis-like epidermis alterations. Here, we investigated the relationship between these mediators. Although IL-20 was not able to regulate IL-22 production, IL-22 induced IL-20 mRNA and protein in human keratinocytes. However, IL-22 had only a minimal effect, if any, on IL-19 and IL-26. Cutaneous IL-20 was also elevated in mice following IL-22 application. Accordingly, some of IL-22's effects on differentiation-regulating genes were partially mediated by an endogenous, secreted protein and attenuated by anti-IL-20 Ab. Like IL-22, IL-17A and TNF-alpha induced IL-20 in keratinocytes, whereas IFN-gamma and IL-20 itself did not. Furthermore, IL-17A and TNF-alpha individually strengthened the IL-22-induced IL-20 production. In lesional skin of psoriasis patients, highly elevated IL-20 levels strongly correlated with IL-22, and to a lesser extent, with IL-17A and TNF-alpha. As previously shown for IL-22, IL-20 blood levels correlated with the disease severity, although with a lower significance. This study demonstrates that a T-cell mediator induces a tissue cell mediator with similar effects to its own and therefore suggests the existence of a novel type of pathogenetic cascade.
authors.affiliation: Interdisciplinary Department of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.forename: Ellen
authors.initials: E
authors.lastname: Witte
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Warszawska
authors.forename: Gundula
authors.initials: G
authors.lastname: Schulze-Tanzil
authors.forename: Katrin
authors.initials: K
authors.lastname: Witte
authors.forename: Sandra
authors.initials: S
authors.lastname: Philipp
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kunz
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Döcke
authors.forename: Khusru
authors.initials: K
authors.lastname: Asadullah
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011565:Psoriasis / Q000097:blood / Q000276:immunology / Q000473:pathology; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22; C422042:interleukin 20