A single intradermal injection of IFN-γ induces an inflammatory state in both non-lesional psoriatic and healthy skin

Leanne M. Johnson-Huang, Mayte Suárez-Fariñas, Katherine C. Pierson, Judilyn Fuentes-Duculan, Inna Cueto, Tim Lentini, Mary Sullivan-Whalen, Patricia Gilleaudeau, James G. Krueger, Asifa S. Haider, Michelle A. Lowes

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55 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1177-1187
Number of pages11
JournalJournal of Investigative Dermatology
Volume132
Issue number4
DOIs
StatePublished - Apr 2012

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Johnson-Huang, L. M., Suárez-Fariñas, M., Pierson, K. C., Fuentes-Duculan, J., Cueto, I., Lentini, T., Sullivan-Whalen, M., Gilleaudeau, P., Krueger, J. G., Haider, A. S., & Lowes, M. A. (2012). A single intradermal injection of IFN-γ induces an inflammatory state in both non-lesional psoriatic and healthy skin. Journal of Investigative Dermatology, 132(4), 1177-1187. https://doi.org/10.1038/jid.2011.458