Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris.
Psoriasis is a type I-deviated disease characterized by the presence of interferon (IFN)-gamma and multiple IFN-related inflammatory genes in lesions. Because interleukin (IL)-23 is now recognized to play a role in the recruitment of inflammatory cells in a T helper cell (Th)1-mediated disease, we examined psoriasis skin lesions for production of this newly described cytokine. IL-23 is composed of two subunits: a unique p19 subunit and a p40 subunit shared with IL-12. We found a reliable increase in p19 mRNA by quantitative reverse transcription polymerase chain reaction in lesional skin compared with nonlesional skin (22.3-fold increase; P = 0.001). The p40 subunit, shared by IL-12 and IL-23, increased by 11.6-fold compared with nonlesional skin (P = 0.003), but the IL-12 p35 subunit was not increased in lesional skin. IL-23 was expressed mainly by dermal cells and increased p40 immunoreactivity was visualized in large dermal cells in the lesions. Cell isolation experiments from psoriatic tissue showed strong expression of p19 mRNA in cells expressing monocyte (CD14+ CD11c+ CD83-) and mature dendritic cell (DC) markers (CD14- CD11c+ CD83+), whereas in culture, the mRNAs for p40 and p19 were strongly up-regulated in stimulated monocytes and monocyte-derived DCs, persisting in the latter for much longer periods than IL-12. Our data suggest that IL-23 is playing a more dominant role than IL-12 in psoriasis, a Th1 type of human inflammatory disease.
Lee
Edmund
E
Laboratory for Investigative Dermatology, The Rockefeller University Hospital, P.O. Box 178, 1230 York Avenue, New York, NY 10021, USA. leee@rockefeller.edu
Trepicchio
William L
WL
Oestreicher
Judith L
JL
Pittman
Debra
D
Wang
Frank
F
Chamian
Francesca
F
Dhodapkar
Madhav
M
Krueger
James G
JG
D000328:Adult; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000276:immunology* / Q000473:pathology; D014158:Transcription, Genetic
C508840:IL23A protein, human; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D020033:Protein Isoforms; D012333:RNA, Messenger; D018664:Interleukin-12