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Cytometric analysis reveals an association between allergen-responsive natural killer cells and human peanut allergy
Xiaoying Zhou, Wong Yu, Diane M. Dunham, Jackson P. Schuetz, Catherine A. Blish, Rosemarie H. DeKruyff, Kari C. Nadeau
Xiaoying Zhou, Wong Yu, Diane M. Dunham, Jackson P. Schuetz, Catherine A. Blish, Rosemarie H. DeKruyff, Kari C. Nadeau
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Research Article Immunology

Cytometric analysis reveals an association between allergen-responsive natural killer cells and human peanut allergy

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Abstract

Food allergies are a leading cause of anaphylaxis, and allergen-specific immune responses in both the innate and the adaptive immune system play key roles in its pathogenesis. We conducted a comprehensive phenotypic and functional investigation of immune cell responses from nonallergic (NA) and peanut allergic (PA) participants cultured with media alone or peanut protein and found, surprisingly, that NK cell activation was strongly associated with the immune response to allergen in PA participants. Peanut-responsive NK cells manifested a distinct expression pattern in PA participants compared with NA participants. Allergen-activated NK cells expressed both Th2 and immune regulatory cytokines, hinting at a potential functional role in mediating and regulating the Th2 allergic response. Depletion of CD3+ T cells attenuated the response of NK cells to peanut-allergen stimulation, suggesting that peanut-responsive NK cells are T cell dependent. We also showed that oral immune therapy was associated with decreased NK responses to peanut allergen stimulation in vitro. These results demonstrate that NK cells are associated with the food-allergic immune response, and the magnitude of this mobilized cell population suggests that they play a functional role in allergic immunity.

Authors

Xiaoying Zhou, Wong Yu, Diane M. Dunham, Jackson P. Schuetz, Catherine A. Blish, Rosemarie H. DeKruyff, Kari C. Nadeau

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Figure 9

OIT is associated with diminished activation of NK cells from PA participants cultured with peanut protein.

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OIT is associated with diminished activation of NK cells from PA partici...
(A) Schematic of the timeline of the clinical study design, showing omalizumab injections from weeks 1–16 and OIT from weeks 8–30. Blood samples were drawn at baseline and week 30. (B) Mass cytometric gating strategy for NK cell subsets. (C) Total NK cells (left), CD56dimCD16+ NK cells (middle) and CD56brightCD16dim/– NK cells (right) as a percentage of total PBMCs cultured with or without peanut protein at baseline and week 30 after OIT from 23 PA participants. (D) Representative flow cytometry plots gated on NK cells showing the effect of OIT on CD69+NK, NKp30+NK, and CD107a+NK for 1 PA participant. (E) Percentage of CD69+NK in NK cells shown for 6 PA participants before and during OIT. (F) The degree of increase in the CD69+ NK cells in response to peanut stimulation was calculated by subtracting the percentage of this population in the unstimulated sample from that in the corresponding stimulated sample. The degree of peanut-induced increase in CD69+ NK cells was examined before and during OIT for 6 PA participants. (G) Percentage of NKp30+NK (left) and CD107a+NK (right) in NK cells shown for 6 PA participants before and during OIT. Since the PBMC sample from 1 of the 6 PA participants at the 300 mg peanut OIT was not available, we only have 5 readouts at this timepoint. Box plots indicate the IQR and median; whiskers extend to the farthest data point within a maximum of 1.5 × IQR. Paired sample sets were analyzed using a 2-sided Wilcoxon signed rank test. Each pair of points connected by a line represents 1 participant. Unpaired sample sets were analyzed using a 2-sided Wilcoxon rank sum test. The stars indicate the P values, **P < 0.01.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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