Elevated NK-cell transcriptional signature and dysbalance of resting and activated NK cells in atopic dermatitis.
J Allergy Clin Immunol
; 147(5): 1959-1965.e2, 2021 05.
Article
in En
| MEDLINE
| ID: mdl-33390269
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Killer Cells, Natural
/
Dermatitis, Atopic
/
Transcriptome
Type of study:
Qualitative_research
Limits:
Adult
/
Humans
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2021
Document type:
Article
Affiliation country:
Alemania