January 5, 2004 | Edmund Lee, William L. Trepicchio, Judith L. Oestreicher, Debra Pittman, Frank Wang, Francesca Chamian, Madhav Dhodapkar, and James G. Krueger
Psoriasis vulgaris is a T-cell-driven, type I (IFN-γ-producing) inflammatory disease characterized by elevated levels of IFN-γ, TNF-α, and various interleukins and chemokines in lesional skin. This study investigated the expression of interleukin (IL)-23 subunits p19 and p40 in psoriatic skin lesions. IL-23 is a heterodimer composed of p19 and p40 subunits, with p40 shared with IL-12. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) revealed a significant increase in p19 mRNA (22.3-fold) and p40 mRNA (11.6-fold) in lesional skin compared to nonlesional skin, while IL-12 p35 mRNA was not increased. Immunohistochemistry showed p40 protein in dermal cells, and p19 was enriched in monocytes and mature dendritic cells (DCs). Cell isolation experiments confirmed strong p19 mRNA expression in monocytes and DCs, with p40 and p19 mRNAs strongly up-regulated in stimulated monocytes and monocyte-derived DCs. These findings suggest that IL-23 plays a more dominant role than IL-12 in psoriasis, a Th1-type inflammatory disease. IL-23 is expressed mainly by dermal cells and is involved in the recruitment of inflammatory cells. The sustained expression of IL-23 subunits in mature DCs contrasts with the transient expression of p35 mRNA in maturing DCs. The study highlights the importance of IL-23 in psoriasis, with potential therapeutic implications for inflammatory skin diseases.Psoriasis vulgaris is a T-cell-driven, type I (IFN-γ-producing) inflammatory disease characterized by elevated levels of IFN-γ, TNF-α, and various interleukins and chemokines in lesional skin. This study investigated the expression of interleukin (IL)-23 subunits p19 and p40 in psoriatic skin lesions. IL-23 is a heterodimer composed of p19 and p40 subunits, with p40 shared with IL-12. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) revealed a significant increase in p19 mRNA (22.3-fold) and p40 mRNA (11.6-fold) in lesional skin compared to nonlesional skin, while IL-12 p35 mRNA was not increased. Immunohistochemistry showed p40 protein in dermal cells, and p19 was enriched in monocytes and mature dendritic cells (DCs). Cell isolation experiments confirmed strong p19 mRNA expression in monocytes and DCs, with p40 and p19 mRNAs strongly up-regulated in stimulated monocytes and monocyte-derived DCs. These findings suggest that IL-23 plays a more dominant role than IL-12 in psoriasis, a Th1-type inflammatory disease. IL-23 is expressed mainly by dermal cells and is involved in the recruitment of inflammatory cells. The sustained expression of IL-23 subunits in mature DCs contrasts with the transient expression of p35 mRNA in maturing DCs. The study highlights the importance of IL-23 in psoriasis, with potential therapeutic implications for inflammatory skin diseases.