title: Prominent production of IL-20 by CD68+/CD11c+ myeloid-derived cells in psoriasis: Gene regulation and cellular effects.
abstract: 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 beta2 integrins, and incubation with tumor necrosis factor-alpha stimulated expression in these cells. IL-20 receptor (IL-20R)alpha and IL-20Rbeta 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-gamma-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.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York 10021, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Wang
authors.forename: Edmund
authors.initials: E
authors.lastname: Lee
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
authors.forename: Asifa S
authors.initials: AS
authors.lastname: Haider
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.forename: Maria Veronica
authors.initials: MV
authors.lastname: Abello
authors.forename: Francesca
authors.initials: F
authors.lastname: Chamian
authors.forename: Irma
authors.initials: I
authors.lastname: Cardinale
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000328:Adult; D000077944:Alefacept; D015703:Antigens, CD / Q000032:analysis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis*; D039521:CD11c Antigen / Q000032:analysis*; D018801:CD2 Antigens / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D039641:Integrin beta Chains / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D007378:Interleukins / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015603:Keratinocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007962:Leukocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011565:Psoriasis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D018123:Receptors, Interleukin / Q000032:analysis / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012867:Skin / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097382:CD68 Molecule
chemical_list: D000077944:Alefacept; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039521:CD11c Antigen; D018801:CD2 Antigens; D039641:Integrin beta Chains; D007371:Interferon-gamma; D007378:Interleukins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C492510:interleukin-20 receptor; C422042:interleukin 20