IL-1RL2 and its ligands contribute to the cytokine network in psoriasis

• Published in: The Journal of immunology (1950) Vol. 185; no. 7; pp. 4354 - 4362
• Main Authors: Blumberg, Hal, Dinh, Huyen, Dean, Jr, Charles, Trueblood, Esther S, Bailey, Keith, Shows, Donna, Bhagavathula, Narasimharao, Aslam, Muhammad Nadeem, Varani, James, Towne, Jennifer E, Sims, John E
• Format: Journal Article
• Language: English
• Published: United States 01.10.2010
• Subjects: Animals; Cytokines - immunology; Disease Models, Animal; Gene Expression; Gene Expression Profiling; Humans; Immunohistochemistry; Interleukin-1 - immunology; Interleukin-1 - metabolism; Interleukin-18 Receptor alpha Subunit - immunology; Interleukin-18 Receptor alpha Subunit - metabolism; Ligands; Mice; Mice, Inbred C57BL; Mice, SCID; Mice, Transgenic; Polymerase Chain Reaction; Psoriasis - immunology; Psoriasis - metabolism; Psoriasis - pathology; Receptors, Interleukin-1 - immunology; Receptors, Interleukin-1 - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1000313

Psoriasis is a common immune-mediated disease in European populations; it is characterized by inflammation and altered epidermal differentiation leading to redness and scaling. T cells are thought to be the main driver, but there is also evidence for an epidermal contribution. In this article, we show that treatment of mouse skin overexpressing the IL-1 family member, IL-1F6, with phorbol ester leads to an inflammatory condition with macroscopic and histological similarities to human psoriasis. Inflammatory cytokines thought to be important in psoriasis, such as TNF-α, IL-17A, and IL-23, are upregulated in the mouse skin. These cytokines are induced by and can induce IL-1F6 and related IL-1 family cytokines. Inhibition of TNF or IL-23 inhibits the increased epidermal thickness, inflammation, and cytokine production. Blockade of IL-1F6 receptor also resolves the inflammatory changes in human psoriatic lesional skin transplanted onto immunodeficient mice. These data suggest a role for IL-1F family members in psoriasis.