Interferon and biologic signatures in dermatomyositis skin

Specificity and heterogeneity across diseases

David Wong, Bory Kea, Rob Pesich, Brandon W. Higgs, Wei Zhu, Patrick Brown, Yihong Yao, David Fiorentino

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Background: Dermatomyositis (DM) is an autoimmune disease that mainly affects the skin, muscle, and lung. The pathogenesis of skin inflammation in DM is not well understood. Methodology and Findings: We analyzed genome-wide expression data in DM skin and compared them to those from healthy controls. We observed a robust upregulation of interferon (IFN)-inducible genes in DM skin, as well as several other gene modules pertaining to inflammation, complement activation, and epidermal activation and differentiation. The interferon (IFN)-inducible genes within the DM signature were present not only in DM and lupus, but also cutaneous herpes simplex-2 infection and to a lesser degree, psoriasis. This IFN signature was absent or weakly present in atopic dermatitis, allergic contact dermatitis, acne vulgaris, systemic sclerosis, and localized scleroderma/morphea. We observed that the IFN signature in DM skin appears to be more closely related to type I than type II IFN based on in vitro IFN stimulation expression signatures. However, quantitation of IFN mRNAs in DM skin shows that the majority of known type I IFNs, as well as IFN g, are overexpressed in DM skin. In addition, both IFN-beta and IFN-gamma (but not other type I IFN) transcript levels were highly correlated with the degree of the in vivo IFN transcriptional response in DM skin. Conclusions and Significance: As in the blood and muscle, DM skin is characterized by an overwhelming presence of an IFN signature, although it is difficult to conclusively define this response as type I or type II. Understanding the significance of the IFN signature in this wide array of inflammatory diseases will be furthered by identification of the nature of the cells that both produce and respond to IFN, as well as which IFN subtype is biologically active in each diseased tissue.

Original languageEnglish (US)
Article numbere29161
JournalPLoS One
Volume7
Issue number1
DOIs
StatePublished - Jan 3 2012
Externally publishedYes

Fingerprint

dermatomyositis
Dermatomyositis
interferons
skin (animal)
Interferons
Skin
Genes
Localized Scleroderma
Interferon Type I
Systemic Scleroderma
Interferon-beta
interferon-gamma
Interferon-gamma
Muscle
scleroderma (skin disease)
Chemical activation
Dermatitis
inflammation
Inflammation
acne

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Interferon and biologic signatures in dermatomyositis skin : Specificity and heterogeneity across diseases. / Wong, David; Kea, Bory; Pesich, Rob; Higgs, Brandon W.; Zhu, Wei; Brown, Patrick; Yao, Yihong; Fiorentino, David.

In: PLoS One, Vol. 7, No. 1, e29161, 03.01.2012.

Research output: Contribution to journalArticle

Wong, David ; Kea, Bory ; Pesich, Rob ; Higgs, Brandon W. ; Zhu, Wei ; Brown, Patrick ; Yao, Yihong ; Fiorentino, David. / Interferon and biologic signatures in dermatomyositis skin : Specificity and heterogeneity across diseases. In: PLoS One. 2012 ; Vol. 7, No. 1.
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