Increased Expression of Interleukin 23 p19 and p40 in Lesional Skin of Patients with Psoriasis Vulgaris

By Edmund Lee, W. Trepicchio, J. Oestreicher, D. Pittman, Frank Wang, Francesca Chamian, Madhav Dhodapkar, J. Krueger. Journal of Experimental Medicine, 2004

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Psoriasis is a type I–deviated disease characterized by the presence of interferon (IFN)-γ 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.

Subfields: Dermatology, Immunology, Physiology

View Paper: https://www.semanticscholar.org/paper/94d12800488ccd98aadbc0ceacf81a44b848a2e9

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Citations in the corpus

Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. (2011, background): “The Th17/ IL-23 pathway is highly increased in psoriatic skin lesions (Lee et al., 2004; Lowes et al., 2008; Di Cesare et al., 2009) and is central to psoriasis pathogenesis, as genetic CCL20”
Th17 cells in human disease (2008, background): “studies have now shown that the p40 subunit and the IL-23specific p19 subunit, not the IL-12-specific p35 subunit, are highly expressed in monocytes and DCs in psoriatic skin lesions (20, 63, 65, 66).”
Development, cytokine profile and function of human interleukin 17–producing helper T cells (2007, background): “Published data indicate that transcripts encoding IL-23p19 and IL-12p40, the subunits that compose human IL-23, are expressed during human psoriasi”
The biological functions of T helper 17 cell effector cytokines in inflammation. (2008, neutral): “Recently, a critical role of IL-23 in the pathogenesis of psoriasis was indicated on the basis of both genetic-association study and human clinical data (Cargill et al., 2007; Kauffman et al., 2004; Krueger et al., 2007; Lee et al., 2004).”
Th17 cell differentiation: the long and winding road. (2008, positive): “The Th17 factors RORgt, IL-17, IL-22, and IL-23 mRNA are all elevated in psoriatic lesional skin ( Lee et al., 2004; Teunissen et al., 1998; Wilson et al., 2007; Wolk et al., 2004).”
Review of ustekinumab, an interleukin-12 and interleukin-23 inhibitor used for the treatment of plaque psoriasis (2010, positive): “Dovepress Immunohistochemical analyses have revealed p40 and p19 (subunits of IL-23) protein expression in dermal dendritic cells and keratinocytes of lesional psoriatic skin.(31,32) Genetic studies have shown that a single nucleotide polymorphism in p40 (the common subunit of both IL-12 and IL-23)(”
The IL-23/Th17 axis in the immunopathogenesis of psoriasis. (2009, result): “These data were complemented in humans by Lee et al. (2004) showing overexpression of IL-23p19 and IL-12p40, in the absence of IL-12p35, at the mRNA level in psoriatic skin lesions, when compared with that in uninvolved skin.”