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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 4

NK cell subsets are an important component for the identification of the allergic immune response by Lasso logistic regression or random forest analyses.

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NK cell subsets are an important component for the identification of the...
(A) PCA of 17 cell subsets (6 NK cell subsets and 11 Th2 cell subsets) using data from 26 NA and 22 PA participants, cultured with or without peanut protein. The percentage variance explained by PC1 and PC2 are indicated. Each point represents 1 sample. (B) Euclidean distances computed based on 17 NK and Th2 cell subsets. The median values (with 95% CI) of the Euclidean distances between sample pairs are shown (left), and the median distances are displayed as a heat map (right). (C) Receiver operating characteristic (ROC) curves show the AUC, sensitivity and specificity of Lasso regression models for the training set (top) and test set (bottom). Left (data set 1) shows PBMCs from PA participants, peanut stimulated and unstimulated. Right (data set 2) shows peanut stimulated PBMCs from PA and NA participants. (D) Lasso regression model plots show the relative contribution (nonzero coefficient values) of different cell subsets in distinguishing peanut stimulated versus unstimulated PBMCs from PA participants (left), or peanut stimulated PBMCs from NA versus PA participants (right). The less contributive variables shrink to zero and are removed from the models. (E) Random forest (RF) models (using proximity scores from the training data set) were used to generate MDS plots that distinguish peanut stimulated versus unstimulated PBMCs from PA participants (top left), or peanut stimulated PBMCs from PA versus NA participants (top right). The RF models were used on the test data set to generate ROC curves showing the AUC, sensitivity and specificity. Bottom left shows peanut-stimulated versus unstimulated PBMCs from PA participants; bottom right shows peanut-stimulated PBMCs from PA versus NA participants. (F) Relative importance of different cell subsets used by the RF model to distinguish peanut-stimulated versus unstimulated PBMCs from PA participants (left), or peanut stimulated PBMCs from NA versus PA participants (right).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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