Elevated NK-cell transcriptional signature and dysbalance of resting and activated NK cells in atopic dermatitis

Association of KIR2DL5, KIR2DS5, and KIR2DS1 allelic variation and atopic dermatitis

“…Two recent studies described the potential physiology of an association between AD and NK cell function and number 11 , 16 . In a cohort of individuals with moderate to severe AD by Mack et al , individuals with AD had fewer circulating NK cells that are more homogenous than expected 11 .…”

“…Some of the subjects evaluated by Mack et al were from the GAD cohort. Mobus et al evaluated NK cells using skin transcriptomics in a likely White European group with moderate to severe AD 16 . These investigations noted an increased number of NK cells in AD lesional skin as compared to AD non-lesional skin or healthy control skin 16 .…”

“…AD is associated with T-cell dysregulation 7 – 10 . Several recent studies, have associated AD with altered numbers of natural killer (NK) cells and diminished NK cell function 11 – 16 . NK cell function is directly associated with Human Leukocyte Antigen (HLA) Class I and NK cell surface receptors like the killer cell Ig-like receptor family (KIR) as well as other NK cell surface receptors 17 – 22 .…”

Immune cell profiling reveals natural killer and T cell subpopulations to be associated with atopic dermatitis severity

“…These results support an increased NK cell apoptosis in the blood or an increased extravasation in the inflamed skin. 5 The frequency of a CD38 + CD69+ NK cell subset, resembling most probably activated NK cells after tissue egress, was increased in ADm, an effect much more pronounced in AD (Figure 1D) and indicating NK cell activation in the AD skin, 6 for example, by driving Th2-cytokines in keratinocytes. 4 Besides Th2 also increased frequencies of activated T helper effector memory cells (CD3 + CD4 + CD8-CD45RO + CD45RA-CCR7-CD127-CD27 + HLADR) and activated Treg's (CD3 + CD4 + CD25hi CD127-CD38 + HLADR) were identified in all AD samples, which could be confirmed by manual gating (Figure 1E), with additional subtle differences on other CD4+ and CD8+ T cell subpopulations.…”

Atopic Dermatitis Is Associated with Preeclampsia and Endometriosis

“…NK cell function has been shown to be associated with atopic dermatitis (AD), with patients with AD usually having decreased circulating numbers of NK cells but increasing lesional skin numbers of NK cells ( Kabashima and Weidinger, 2020 ; Mack et al., 2020 ; Möbus et al., 2021 ; Sun et al., 2021 ). An important regulator of NK cell function are KIR genes, which can have either inhibitory or activating effects on NK cells ( Pende et al., 2019 ).…”