In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin.
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.
Piskin
Gamze
G
Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. g.piskin@amc.uva.nl
Sylva-Steenland
Regien M R
RM
Bos
Jan D
JD
Teunissen
Marcel B M
MB
D000276:Adjuvants, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D020405:Dermis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019281:Dimerization; D004817:Epidermis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D000276:Adjuvants, Immunologic; C508840:IL23A protein, human; D018836:Inflammation Mediators; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D012333:RNA, Messenger; D007371:Interferon-gamma