TY - JOUR
T1 - Prominent production of IL-20 by CD68+/CD11c+ Myeloid-derived cells in psoriasis
T2 - Gene regulation and cellular effects
AU - Wang, Frank
AU - Lee, Edmund
AU - Lowes, Michelle A.
AU - Haider, Asifa S.
AU - Fuentes-Duculan, Judilyn
AU - Abello, Maria Veronica
AU - Chamian, Francesca
AU - Cardinale, Irma
AU - Krueger, James G.
N1 - Funding Information:
We thank Madhav Dhodapkar and the Laboratory for Tumor Immunology and Immunotherapy at The Rockefeller University for isolation of monocytes/DCs (particularly Joseph Krasovsky for technical assistance), Polina Bulkina for assistance with manuscript preparation, and Inna Novitskaya and Toyoko Kikuchi for additional technical assistance. This research was supported in part by a General Clinical Research Center grant (M01-RR00102) from the National Center for Research Resources at the National Institutes of Health. J.G.K. is supported by NIH Grants R01 AI-49572 and AI-49832.
PY - 2006/7
Y1 - 2006/7
N2 - We assessed expression of IL-20 and its receptors in psoriasis, given the recent implication of IL-20 in epidermal hyperplasia. Psoriatic lesional (LS) skin consistently expressed more IL-20 mRNA than nonlesional (NL) skin. Immunoreactivity to IL-20 protein was greater in LS tissue and mainly localized to infiltrating CD68+/CD11c+ (myeloid-derived) dermal leukocytes. Because this contrasted with earlier reports of a keratinocyte source, we assessed IL-20 mRNA expression in a variety of cells in vitro, and confirmed a myeloid-derived cellular source (monocytes). Plastic adhesion, activation of β2 integrins, and incubation with tumor necrosis factor-α stimulated expression in these cells. IL-20 receptor (IL-20R)α and IL-20Rβ mRNA was decreased in LS versus NL skin, which also contrasted with earlier findings. To investigate the relationship between IL-20 and disease activity, we examined psoriasis patients treated with the CD2-targeted agent alefacept. In therapeutic responders, lesional IL-20 mRNA decreased to NL levels, suggesting that CD2+ leukocytes may proximally regulate IL-20. Finally, to assess IL-20 function, we used microarrays to screen IL-20-treated keratinocytes, which demonstrated upregulation of disease-related and IFN-γ-induced genes. Hence, IL-20 may influence inflammation through IFN-like effects. Together, these data indicate that IL-20 may be an important effector cytokine in psoriasis, and that its inhibition may represent a potential therapeutic target.
AB - We assessed expression of IL-20 and its receptors in psoriasis, given the recent implication of IL-20 in epidermal hyperplasia. Psoriatic lesional (LS) skin consistently expressed more IL-20 mRNA than nonlesional (NL) skin. Immunoreactivity to IL-20 protein was greater in LS tissue and mainly localized to infiltrating CD68+/CD11c+ (myeloid-derived) dermal leukocytes. Because this contrasted with earlier reports of a keratinocyte source, we assessed IL-20 mRNA expression in a variety of cells in vitro, and confirmed a myeloid-derived cellular source (monocytes). Plastic adhesion, activation of β2 integrins, and incubation with tumor necrosis factor-α stimulated expression in these cells. IL-20 receptor (IL-20R)α and IL-20Rβ mRNA was decreased in LS versus NL skin, which also contrasted with earlier findings. To investigate the relationship between IL-20 and disease activity, we examined psoriasis patients treated with the CD2-targeted agent alefacept. In therapeutic responders, lesional IL-20 mRNA decreased to NL levels, suggesting that CD2+ leukocytes may proximally regulate IL-20. Finally, to assess IL-20 function, we used microarrays to screen IL-20-treated keratinocytes, which demonstrated upregulation of disease-related and IFN-γ-induced genes. Hence, IL-20 may influence inflammation through IFN-like effects. Together, these data indicate that IL-20 may be an important effector cytokine in psoriasis, and that its inhibition may represent a potential therapeutic target.
UR - http://www.scopus.com/inward/record.url?scp=33745209428&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745209428&partnerID=8YFLogxK
U2 - 10.1038/sj.jid.5700310
DO - 10.1038/sj.jid.5700310
M3 - Article
C2 - 16645593
AN - SCOPUS:33745209428
SN - 0022-202X
VL - 126
SP - 1590
EP - 1599
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 7
ER -