CLINICAL AND LABORATORY INVESTIGATIONS DOI 10.1111/j.1365-2133.2005.06800.x The dynamics of gene expression of interleukin-19 and interleukin-20 and their receptors in psoriasis K. Otkjaer, K. Kragballe, A.T. Funding, J.T. Clausen, P.L. Noerby, T. Steiniche* and L. Iversen Departments of Dermatology and *Pathology and Anatomy, Aarhus Hospital, P.P. Ørumsgade 11, University of Aarhus, DK-8000 Aarhus C, Denmark  Discovery, Novo Nordisk, DK-2880 Bagsværd, Denmark Correspondence Kristian Otkjaer MD. E-mail: otkjaer@ki.au.dk Accepted for publication 5 March 2005 Key words: IL-19, IL-20, IL-20Ra, IL-20Rb, IL-22Ra, psoriasis Conflicts of interest: None declared. Summary Background Interleukin (IL)-20 and IL-19 are recently discovered members of the IL-10 family of cytokines. The skin of transgenic mice overexpressing IL-20 shows histological changes resembling some of those seen in psoriasis, i.e. thickened epidermis, hyperkeratosis and a compact stratum corneum. IL-19 and IL-20, as well as their receptor complexes, IL-20Ra ⁄ IL-20Rb and IL-22Ra ⁄ IL-20Rb, are expressed in human skin. Objectives To study the dynamics of IL-19 and IL-20 gene expression as well as the expression of their receptor subunits in psoriatic skin lesions. Methods Punch biopsies from patients with plaque-type psoriasis were collected before, during and after 28 days of treatment with either calcipotriol or ciclospo- rin (CsA). IL-20, IL-19, IL-20Ra, IL-20Rb and IL-22Ra mRNA expression were determined by quantitative reverse transcriptase–polymerase chain reaction. Results We found IL-19 and IL-20 mRNA expression in lesional psoriatic skin to be strongly upregulated compared with nonlesional psoriatic skin by a factor of 65 and 22, respectively. In contrast to previous reports, IL-20Ra and IL-20Rb mRNA levels showed a modest but statistically significant decrease in lesional psoriatic skin compared with nonlesional psoriatic skin. During treatment with calcipotriol or CsA, IL-19 and IL-20 mRNA levels decrease in accordance with the clinical improvement of psoriasis. Neither IL-19, IL-20, nor receptor subunit mRNA expression in lesional psoriatic skin reaches the levels of nonlesional skin during this short-term treatment. These findings are in line with the residual dis- ease activity observed at the end of treatment. Conclusions The increased IL-19 and IL-20 mRNA expression levels in lesional pso- riatic skin suggest that these two cytokines play a role in the pathogenesis of pso- riasis. An imbalance in the receptor complexes for IL-19 and IL-20 might contribute to their suspected pathogenic effects. Expression of interleukin (IL)-19 and IL-20 and their receptors have been demonstrated in human epidermis. 1,2 Furthermore, IL-19 and IL-20 mRNA expression is increased in psoriatic skin. 2 Overexpression of IL-20 in transgenic mice leads to a psoriasiform phenotype of the skin, 3 whereas the skin of mice overexpressing IL-19 appears normal. 1 Therefore, IL-20 has been ascribed a key role in the pathogenesis of psoriasis. IL-19 and IL-20 are members of the IL-10 family which also comprises IL-22, IL-24 and IL-26. 4 IL-19 and IL-20 were discovered through screening for IL-10-related genes in an Epstein–Barr virus-transformed B-cell cDNA library 5 and a ker- atinocyte cDNA library, respectively. 3 The genes encoding these two cytokines, together with the genes encoding IL-10 and IL-24, are located in a 195-kb region on chromosome 1q32. 3 IL-19 and IL-20 are each other’s closest relatives within the IL-10 family when comparing sequence homology (44Æ1% identity and 52Æ4% similarity). Based on a structural analysis IL-19 was identified as a monomer, and IL-20 is assumed to share a similar three-dimensional structure. 3,6 A heterodimer consisting of an IL-20Ra-subunit and an IL20Rb-subunit was identified as the IL-20 receptor complex, 3 and has also been shown to bind IL-19. 7 Another heterodi- meric receptor complex for IL-20 consisting of IL-22Ra and IL-20Rb has also been described and this receptor complex is not activated by IL-19. 7 At mRNA level IL-20Ra is the most widely expressed receptor subunit. It is expressed in many tis- sues, with the highest level of expression in heart, lung and skin. Testis, ovary and heart express IL-20Ra and IL-20Rb in Ó 2005 British Association of Dermatologists • British Journal of Dermatology 2005 153, pp911–918 911