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: Kerstin Wolk, Ellen Witte, Katarzyna Warszawska, Gundula Schulze-Tanzil, Katrin Witte, Sandra Philipp, Stefanie Kunz, Wolf-Dietrich Döcke, Khusru Asadullah, Hans-Dieter Volk, Wolfram Sterry, Robert Sabat
• Journal: European journal of immunology (Eur J Immunol) Vol. 39 Issue 12 Pg. 3570-81 (Dec 2009) ISSN: 1521-4141 [Electronic] Germany
• PMID: 19830738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-17
• Interleukins
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• interleukin 20

Topics

• Animals
• Cells, Cultured
• Enzyme-Linked Immunosorbent Assay
• Humans
• Immunohistochemistry
• Interleukin-17 (metabolism)
• Interleukins (genetics, metabolism, pharmacology)
• Keratinocytes (cytology, drug effects, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Psoriasis (blood, immunology, pathology)
• RNA Stability (drug effects)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Severity of Illness Index
• Skin (immunology, metabolism, pathology)
• T-Lymphocytes, Helper-Inducer (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Interleukin-22