title: A single intradermal injection of IFN-γ induces an inflammatory state in both non-lesional psoriatic and healthy skin.
abstract: Psoriasis is a chronic, debilitating, immune-mediated inflammatory skin disease. As IFN-γ is involved in many cellular processes, including activation of dendritic cells (DCs), antigen processing and presentation, cell adhesion and trafficking, and cytokine and chemokine production, IFN-γ-producing Th1 cells were proposed to be integral to the pathogenesis of psoriasis. Recently, IFN-γ was shown to enhance IL-23 and IL-1 production by DCs and subsequently induce Th17 cells, which are important contributors to the inflammatory cascade in psoriatic lesions. To determine whether IFN-γ indeed induces the pathways expressed in psoriatic lesions, a single intradermal injection of IFN-γ was administered to an area of clinically normal, non-lesional (NL) skin of psoriasis patients and biopsies were collected 24 hours later. Although there were no visible changes in the skin, IFN-γ induced many molecular and histological features characteristic of psoriatic lesions. IFN-γ increased a number of differentially expressed genes in the skin, including many chemokines concomitant with an influx of T cells and inflammatory DCs. Furthermore, inflammatory DC products tumor necrosis factor (TNF), inducible nitric oxide synthase, IL-23, and TNF-related apoptosis-inducing ligand were present in IFN-γ-treated skin. Thus, IFN-γ, which is significantly elevated in NL skin compared with healthy skin, appears to be a key pathogenic cytokine that can induce many features of the inflammatory cascade of psoriasis.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Johnson-Huang
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Pierson
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.forename: Inna
authors.initials: I
authors.lastname: Cueto
authors.forename: Tim
authors.initials: T
authors.lastname: Lentini
authors.forename: Mary
authors.initials: M
authors.lastname: Sullivan-Whalen
authors.forename: Patricia
authors.initials: P
authors.lastname: Gilleaudeau
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.forename: Asifa S
authors.initials: AS
authors.lastname: Haider
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D002465:Cell Movement; D003713:Dendritic Cells / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D053759:Interleukin-23 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010641:Phenotype; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053759:Interleukin-23; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II