BACKGROUND: Psoriasis is a chronic immune-mediated skin disease, in which interleukins 12 and 23 have been postulated to play a critical role. However, the cellular source of these cytokines in psoriatic lesions are still poorly defined and their relative contribution in inducing skin inflammation has been discussed controversially. OBJECTIVES: To investigate immunoreactivity of the bioactive forms of IL-12 and IL-23 in plaque psoriasis and to characterize the dendritic cell (DC) and macrophage subsets responsible for the production of these cytokines. METHODS: Immunohistochemistry was performed on normal skin (n=11) as well as non-lesional (n=11) and lesional (n=11) skin of patients with plaque psoriasis using monoclonal antibodies targeting the bioactive forms of IL-12 (IL-12p70) and IL-23 (IL-23p19/p40) on serial cryostat sections using the alkaline phosphatase-antialkaline phosphatase. Co-localization of IL-12 and IL-23 with different dendritic cells and macrophage cell markers (CD1a, CD11c, CD14, CD32, CD68, CD163, CD208/DC-LAMP) was performed using double immunofluorescence staining. RESULTS: Immunoreactivity for IL-12 and IL-23 was significantly enhanced in lesional psoriatic skin as compared to non-lesional and normal skin. No difference was observed between IL-12 and IL-23 immunoreactivity in any skin types. Both IL-12 and IL-23 immunoreactivity was readily detected mainly in CD11c+, CD14+, CD32+, CD68+ and some CD163+, DC-LAMP+ cells. IL-12 and occasionally IL-23 were also found in some CD1a+ dendritic cells. In addition, an enhanced expression mainly of IL-23 was observed in keratinocytes. CONCLUSIONS: Bioactive forms of IL-12 and IL-23 are highly expressed in various DC and macrophage subsets and their marked in situ production suggest that both cytokines have crucial pathogenic role in psoriasis.
BACKGROUND:Psoriasis is a chronic immune-mediated skin disease, in which interleukins 12 and 23 have been postulated to play a critical role. However, the cellular source of these cytokines in psoriatic lesions are still poorly defined and their relative contribution in inducing skin inflammation has been discussed controversially. OBJECTIVES: To investigate immunoreactivity of the bioactive forms of IL-12 and IL-23 in plaque psoriasis and to characterize the dendritic cell (DC) and macrophage subsets responsible for the production of these cytokines. METHODS: Immunohistochemistry was performed on normal skin (n=11) as well as non-lesional (n=11) and lesional (n=11) skin of patients with plaque psoriasis using monoclonal antibodies targeting the bioactive forms of IL-12 (IL-12p70) and IL-23 (IL-23p19/p40) on serial cryostat sections using the alkaline phosphatase-antialkaline phosphatase. Co-localization of IL-12 and IL-23 with different dendritic cells and macrophage cell markers (CD1a, CD11c, CD14, CD32, CD68, CD163, CD208/DC-LAMP) was performed using double immunofluorescence staining. RESULTS: Immunoreactivity for IL-12 and IL-23 was significantly enhanced in lesional psoriatic skin as compared to non-lesional and normal skin. No difference was observed between IL-12 and IL-23 immunoreactivity in any skin types. Both IL-12 and IL-23 immunoreactivity was readily detected mainly in CD11c+, CD14+, CD32+, CD68+ and some CD163+, DC-LAMP+ cells. IL-12 and occasionally IL-23 were also found in some CD1a+ dendritic cells. In addition, an enhanced expression mainly of IL-23 was observed in keratinocytes. CONCLUSIONS: Bioactive forms of IL-12 and IL-23 are highly expressed in various DC and macrophage subsets and their marked in situ production suggest that both cytokines have crucial pathogenic role in psoriasis.
Authors: Michael N Alonso; Michael T Wong; Angela L Zhang; Daniel Winer; Megan M Suhoski; Lorna L Tolentino; Juliana Gaitan; Matthew G Davidson; Tiffany H Kung; David M Galel; Kari C Nadeau; Jinah Kim; Paul J Utz; Kalle Söderström; Edgar G Engleman Journal: Blood Date: 2011-08-02 Impact factor: 22.113
Authors: Judilyn Fuentes-Duculan; Mayte Suárez-Fariñas; Lisa C Zaba; Kristine E Nograles; Katherine C Pierson; Hiroshi Mitsui; Cara A Pensabene; Julia Kzhyshkowska; James G Krueger; Michelle A Lowes Journal: J Invest Dermatol Date: 2010-06-17 Impact factor: 8.551
Authors: Giulia Tonel; Curdin Conrad; Ute Laggner; Paola Di Meglio; Katarzyna Grys; Terrill K McClanahan; Wendy M Blumenschein; Jian-Zhong Qin; Hong Xin; Elizabeth Oldham; Robert Kastelein; Brian J Nickoloff; Frank O Nestle Journal: J Immunol Date: 2010-10-18 Impact factor: 5.422
Authors: Christian Wohn; Julia L Ober-Blöbaum; Stefan Haak; Stanislav Pantelyushin; Cheolho Cheong; Sonja P Zahner; Sabina Onderwater; Marius Kant; Heike Weighardt; Bernhard Holzmann; Boris Reizis; Burkhard Becher; Errol P Prens; Björn E Clausen Journal: Proc Natl Acad Sci U S A Date: 2013-06-10 Impact factor: 11.205