A Single Intradermal Injection of IFN-γ Induces an Inflammatory State in Both Non-Lesional Psoriatic and Healthy Skin

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...

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Bibliographic Details
Published in:Journal of investigative dermatology 2012-04, Vol.132 (4), p.1177-1187
Main Authors: Johnson-Huang, Leanne M., Suárez-Fariñas, Mayte, Pierson, Katherine C., Fuentes-Duculan, Judilyn, Cueto, Inna, Lentini, Tim, Sullivan-Whalen, Mary, Gilleaudeau, Patricia, Krueger, James G., Haider, Asifa S., Lowes, Michelle A.
Format: Article
Language:English
Subjects:
Biopsy
Case-Control Studies
Cell Movement
Dendritic Cells - pathology
Humans
Inflammation - chemically induced
Inflammation - metabolism
Inflammation - pathology
Injections, Intradermal
Interferon-gamma - administration & dosage
Interferon-gamma - adverse effects
Interferon-gamma - pharmacology
Interleukin-23 - metabolism
Nitric Oxide Synthase Type II - metabolism
Phenotype
Psoriasis - metabolism
Psoriasis - pathology
Skin - drug effects
Skin - metabolism
Skin - pathology
T-Lymphocytes - pathology
TNF-Related Apoptosis-Inducing Ligand - metabolism
Tumor Necrosis Factor-alpha - metabolism
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Summary: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.
ISSN:0022-202X
1523-1747
DOI:10.1038/jid.2011.458