Atopic dermatitis displays stable and dynamic skin transcriptome signatures

J Allergy Clin Immunol. 2021 Jan;147(1):213-223. doi: 10.1016/j.jaci.2020.06.012. Epub 2020 Jun 29.


Background: Skin transcriptome studies in atopic dermatitis (AD) showed broad dysregulation as well as "improvement" under therapy. These observations were mainly made in trials and based on microarray data.

Objectives: Our aim was to explore the skin transcriptome and the impact of systemic treatment in patients of the TREATgermany registry.

Methods: Biopsy specimens from 59 patients with moderate-to-severe AD before and 30 patients 12 weeks after start of systemic treatment (dupilumab [n = 22] or cyclosporine [n = 8]) and from 31 healthy controls were subjected to mRNA sequencing. Differential expression, pathway enrichment, correlation, and coexpression network analysis were conducted.

Results: Both lesional and nonlesional skin showed a stable "core" signature characterized by disturbed epidermal differentiation and activation of IL-31/IL-1 signaling. A second dynamic signature showed progressive enrichment for type 2 inflammation, TH17 signaling, and natural killer cell function. Markers correlated with disease activity have functions in epidermal barrier properties and immune modulation. IL4RA was among the top 3 central dysregulated genes. Cyclosporine led to a more pronounced global transcriptome reversion and normalized TH17 cell/IL23 signaling, whereas dupilumab led to a stronger increase in level of epidermal differentiation markers. Both treatments strongly decreased levels of type 2 markers, but overall the residual profile was still profoundly different from that of healthy skin. Lower levels of IL4RA and IL13 and high IL36A expression were related to a stronger clinical response to dupilumab.

Conclusion: The AD core signature is characterized by dysregulation of genes related to keratinocyte differentiation and itch signaling. A dynamic signature reflects progressive immune responses dominated by type 2 cytokines with an additional role of TH17 and natural killer cell signaling.

Keywords: Atopic dermatitis; RNA-sequencing; cyclosporine; dupilumab; gene expression; residual signatures; transcriptome; type 2 inflammation.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytokines* / genetics
  • Cytokines* / immunology
  • Dermatitis, Atopic* / genetics
  • Dermatitis, Atopic* / immunology
  • Dermatitis, Atopic* / pathology
  • Female
  • Humans
  • Keratinocytes* / immunology
  • Keratinocytes* / pathology
  • Male
  • Middle Aged
  • Skin* / immunology
  • Skin* / pathology
  • Th17 Cells* / immunology
  • Th17 Cells* / pathology
  • Transcriptome / immunology*


  • Cytokines