Altered immune cell profiles and impaired CD4 T-cell activation in single and multi-food allergic adolescents.
Adolescent
CD4-Positive T-Lymphocytes
/ immunology
Case-Control Studies
Child
Cluster Analysis
Cytokines
/ immunology
Egg Hypersensitivity
/ complications
Female
Food Hypersensitivity
/ classification
Humans
Immunophenotyping
Interferon-gamma
/ immunology
Interleukin-6
/ immunology
Leukocytes, Mononuclear
/ immunology
Male
Nut Hypersensitivity
/ complications
Peanut Hypersensitivity
/ complications
Tumor Necrosis Factor-alpha
/ immunology
basic immunology
dendritic cells
food allergy
innate immunity
paediatrics
Journal
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN: 1365-2222
Titre abrégé: Clin Exp Allergy
Pays: England
ID NLM: 8906443
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
10
02
2021
received:
17
12
2020
accepted:
17
02
2021
pubmed:
25
2
2021
medline:
3
2
2022
entrez:
24
2
2021
Statut:
ppublish
Résumé
Approximately 5% of adolescents have a food allergy, with peanut and tree nut allergies the most common. Having two or more food allergies in adolescence also doubles the risk of any adverse food reaction, and is associated with increased dietary and social burden. Investigations of immune function in persistently food allergic children are rare. In the present study, we aimed to investigate the immune mechanisms that underlie food allergy in adolescence. We used high-dimensional flow cytometry, unsupervised computational analysis and functional studies to comprehensively phenotype a range of non-antigen-specific immune parameters in a group of well-characterized adolescents with clinically defined single peanut allergy, multi-food allergy and aged-matched non-food allergic controls. We show that food allergic adolescents have higher circulating proportions of dendritic cells (p = .0084, FDR-adjusted p = .087, median in no FA: 0.63% live cells, in FA: 0.93%), and higher frequency of activated, memory-like Tregs relative to non-food allergic adolescents (p = .011, FDR-adjusted p = .087, median in no FA: 0.49% live cells, in FA: 0.65%). Cytokine profiling revealed that CD3/CD28 stimulated naïve CD4 T cells from food allergic adolescents produced less IL-6 (p = .0020, FDR-adjusted p = .018, median log2 fold change [stimulated/unstimulated] in no FA: 3.03, in FA: 1.92) and TNFα (p = .0044, FDR-adjusted p = .020, median in no FA: 9.16, in FA: 8.64) and may secrete less IFNγ (p = .035, FDR-adjusted p = .11, median in no FA: 6.29, in FA: 5.67) than naïve CD4 T cells from non-food allergic controls. No differences between clinical groups were observed for LPS-stimulated monocyte secretion of cytokines. These results have important implications for understanding the evolution of the immune response in food allergy throughout childhood, revealing that dendritic cell and T-cell signatures previously identified in early life may persist through to adolescence.
Sections du résumé
BACKGROUND
Approximately 5% of adolescents have a food allergy, with peanut and tree nut allergies the most common. Having two or more food allergies in adolescence also doubles the risk of any adverse food reaction, and is associated with increased dietary and social burden. Investigations of immune function in persistently food allergic children are rare.
OBJECTIVE
In the present study, we aimed to investigate the immune mechanisms that underlie food allergy in adolescence.
METHODS
We used high-dimensional flow cytometry, unsupervised computational analysis and functional studies to comprehensively phenotype a range of non-antigen-specific immune parameters in a group of well-characterized adolescents with clinically defined single peanut allergy, multi-food allergy and aged-matched non-food allergic controls.
RESULTS
We show that food allergic adolescents have higher circulating proportions of dendritic cells (p = .0084, FDR-adjusted p = .087, median in no FA: 0.63% live cells, in FA: 0.93%), and higher frequency of activated, memory-like Tregs relative to non-food allergic adolescents (p = .011, FDR-adjusted p = .087, median in no FA: 0.49% live cells, in FA: 0.65%). Cytokine profiling revealed that CD3/CD28 stimulated naïve CD4 T cells from food allergic adolescents produced less IL-6 (p = .0020, FDR-adjusted p = .018, median log2 fold change [stimulated/unstimulated] in no FA: 3.03, in FA: 1.92) and TNFα (p = .0044, FDR-adjusted p = .020, median in no FA: 9.16, in FA: 8.64) and may secrete less IFNγ (p = .035, FDR-adjusted p = .11, median in no FA: 6.29, in FA: 5.67) than naïve CD4 T cells from non-food allergic controls. No differences between clinical groups were observed for LPS-stimulated monocyte secretion of cytokines.
CONCLUSIONS
These results have important implications for understanding the evolution of the immune response in food allergy throughout childhood, revealing that dendritic cell and T-cell signatures previously identified in early life may persist through to adolescence.
Substances chimiques
Cytokines
0
IFNG protein, human
0
IL6 protein, human
0
Interleukin-6
0
TNF protein, human
0
Tumor Necrosis Factor-alpha
0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
674-684Informations de copyright
© 2021 John Wiley & Sons Ltd.
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