Elevated NK-cell transcriptional signature and dysbalance of resting and activated NK cells in atopic dermatitis
Research output: Contribution to journal › Journal article › Research › peer-review
Background: Altered quantities, activity, and composition of natural killer (NK) cells in blood as well as expression changes of genes involved in NK-cell function in skin lesions of patients with atopic dermatitis (AD) were recently reported. Objectives: We sought to comprehensively analyze cutaneous NK-cell transcriptomic signatures in AD, and to examine changes under treatment. Methods: We analyzed NK-cell signatures in skin transcriptome data from 57 patients with moderate to severe AD and 31 healthy controls. In addition, changes after 12 weeks of systemic treatment (dupilumab n = 21, cyclosporine n = 8) were analyzed. Deconvolution of leucocyte fractions was conducted. Immunofluorescence staining of NK cells was performed on paraffin-embedded skin sections. Results: Immunofluorescence staining revealed a relatively high abundance of both NK cells and CD3+CD56+ cells in lesional as compared with nonlesional and healthy skin. Lesional and to a lesser extent nonlesional skin showed a strong upregulation of NK-cell markers together with a dysbalanced expression of inhibitory and activating receptors, which was not reverted under treatment. Digital cytometry showed a decrease in activated and an increase in resting NK cells in both lesional and nonlesional skin, which was reverted by both treatment with dupilumab and cyclosporine. The NK-cell transcriptomic signature remained upregulated after treatment, but there was a shift on the qualitative level, indicating a compositional change in NK-cell subsets toward CD56bright NK cells. Conclusions: Lesional AD skin shows a NK-cell dysregulation, which despite clinical improvement under systemic therapy was only partially reverted, and which may represent a yet underappreciated disease mechanism.
Original language | English |
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Journal | Journal of Allergy and Clinical Immunology |
Volume | 147 |
Issue number | 5 |
Pages (from-to) | 1959-1965.e2 |
ISSN | 0091-6749 |
DOIs | |
Publication status | Published - 2021 |
Externally published | Yes |
- Atopic dermatitis, gene expression, natural killer cells, RNA-Sequencing, skin transcriptome
Research areas
ID: 255882884