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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 8

Cytokine secretion in response to stimulation with peanut allergen was altered in CD3+ T cell–depleted or CD56+ cell-depleted PBMCs compared with mock-depleted PBMCs.

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Cytokine secretion in response to stimulation with peanut allergen was a...
(A) The fold change of peanut-induced cytokines (IL-4, IL-13, IFN-γ, and IL-10) in CD3+ T cell–depleted PBMCs and mock-depleted PBMCs. (B and C) The fold change of peanut-induced cytokines (IL-4, IL-13, IL-9, IL-5, IFN-γ, and IL-10) in PBMCs depleted of CD56+ cells versus mock-depleted PBMCs. The fold change was calculated as the expression levels of these cytokines measured by Luminex assay in the culture with peanut protein (stimulated group) divided by that in the culture with media (unstimulated group). Box plots indicate the IQR and median; whiskers extend to the farthest data point within a maximum of 1.5 × IQR. Unpaired sample sets were analyzed using a 2-sided Wilcoxon rank sum test. **P < 0.01.

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

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