In Vitro and In Situ Expression of IL-23 by Keratinocytes in Healthy Skin and Psoriasis Lesions: Enhanced Expression in Psoriatic Skin

• Published in: Journal of Immunology Vol. 176; no. 3; pp. 1908 - 1915
• Main Authors: Piskin, Gamze, Sylva-Steenland, Regien M. R, Bos, Jan D, Teunissen, Marcel B. M
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.02.2006
• Subjects: Adjuvants, Immunologic - biosynthesis; Adjuvants, Immunologic - genetics; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigen-Presenting Cells - pathology; Cells, Cultured; Dermis - immunology; Dermis - metabolism; Dermis - pathology; Dimerization; Epidermis - immunology; Epidermis - metabolism; Epidermis - pathology; Humans; Immunologic Memory - physiology; Inflammation Mediators - metabolism; Inflammation Mediators - physiology; Interferon-gamma - biosynthesis; Interleukin-23; Interleukin-23 Subunit p19; Interleukins - biosynthesis; Interleukins - genetics; Keratinocytes - immunology; Keratinocytes - metabolism; Keratinocytes - pathology; Psoriasis - immunology; Psoriasis - metabolism; Psoriasis - pathology; RNA, Messenger - metabolism; Skin - immunology; Skin - metabolism; T-Lymphocytes - metabolism
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.176.3.1908

Keratinocytes contribute to cutaneous immune responses through the expression of cytokines. We investigated whether human keratinocytes can express IL-23, a newly defined IFN-gamma-inducing cytokine composed of a unique p19 subunit and a p40 subunit shared with IL-12. Cultured keratinocytes from normal and lesional psoriatic skin were found to express constitutively mRNA for both subunits of IL-23. Low but significant levels of the heterodimeric IL-23 protein could be detected in cell lysates and supernatants from stimulated keratinocytes by immunoblotting and ELISA. Functional analysis showed that these low levels of keratinocyte-derived IL-23 were sufficient to enhance the IFN-gamma production by memory T cells. Immunostaining of skin sections confirmed expression of both subunits of IL-23 by keratinocytes in situ and also revealed expression of this cytokine in the dermal compartment. IL-23 expression was significantly higher in psoriatic lesional skin, compared with normal and psoriatic nonlesional skin. The immunostained preparations of cultured cells and IL-23 levels in culture supernatants did not show any difference between normal and psoriatic keratinocytes indicating no intrinsic aberration of IL-23 expression in keratinocytes from psoriatic skin. Double staining of cytospin preparations demonstrated that IL-23 p19 is also expressed by epidermal Langerhans cells, dermal dendritic cells, and macrophages. Psoriasis is a chronic inflammatory skin disease mediated by IFN-gamma-expressing type 1 memory T cells. As IL-23 is important to activate memory T cells to produce IFN-gamma, its augmented expression of IL-23 by keratinocytes and cutaneous APC may contribute to the perpetuation of the inflammation process in this disease.