Alteration of Immunoregulatory Patterns and Survival Advantage of Key Cell Types in Food Allergic Children
All allergic responses to food indicate the failure of immunological tolerance, but it is unclear why cow’s milk and egg (CME) allergies resolve more readily than reactivity to peanuts (PN). We sought to identify differences between PN and CME allergies through constitutive immune status and respons...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/23/2736 |
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| author | Kamal Ivory Rossella Angotti Mario Messina Denise Bonente Ferdinando Paternostro Massimo Gulisano Claudio Nicoletti |
| author_facet | Kamal Ivory Rossella Angotti Mario Messina Denise Bonente Ferdinando Paternostro Massimo Gulisano Claudio Nicoletti |
| author_sort | Kamal Ivory |
| collection | DOAJ |
| description | All allergic responses to food indicate the failure of immunological tolerance, but it is unclear why cow’s milk and egg (CME) allergies resolve more readily than reactivity to peanuts (PN). We sought to identify differences between PN and CME allergies through constitutive immune status and responses to cognate and non-cognate food antigens. Children with confirmed allergy to CME (<i>n</i> = 6) and PN (<i>n</i> = 18) and non-allergic (NA) (<i>n</i> = 8) controls were studied. Constitutive secretion of cytokines was tested in plasma and unstimulated mononuclear cell (PBMNC) cultures. Blood dendritic cell (DC) subsets were analyzed alongside changes in phenotypes and soluble molecules in allergen-stimulated MNC cultures with or without cytokine neutralization. We observed that in allergic children, constitutively high plasma levels IL-1β, IL-2, IL-4, IL-5 and IL-10 but less IL-12p70 than in non-allergic children was accompanied by the spontaneous secretion of sCD23, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12p70, IFN-γ and TNF-α in MNC cultures. Furthermore, blood DC subset counts differed in food allergy. Antigen-presenting cell phenotypic abnormalities were accompanied by higher B and T cell percentages with more Bcl-2 within CD69<sup>+</sup> subsets. Cells were generally refractory to antigenic stimulation in vitro, but IL-4 neutralization led to CD152 downregulation by CD4<sup>+</sup> T cells from PN allergic children responding to PN allergens. Canonical discriminant analyses segregated non-allergic and allergic children by their cytokine secretion patterns, revealing differences and areas of overlap between PN and CME allergies. Despite an absence of recent allergen exposure, indication of in vivo activation, in vitro responses independent of challenging antigen and the presence of unusual costimulatory molecules suggest dysregulated immunity in food allergy. Most importantly, higher Bcl-2 content within key effector cells implies survival advantage with the potential to mount abnormal responses that may give rise to the manifestations of allergy. Here, we put forward the hypothesis that the lack of apoptosis of key immune cell types might be central to the development of food allergic reactions. |
| first_indexed | 2024-03-09T01:53:36Z |
| format | Article |
| id | doaj.art-30155f6064694e3d8d20c713bf62ff1b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T01:53:36Z |
| publishDate | 2023-11-01 |
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| spelling | doaj.art-30155f6064694e3d8d20c713bf62ff1b2023-12-08T15:13:12ZengMDPI AGCells2073-44092023-11-011223273610.3390/cells12232736Alteration of Immunoregulatory Patterns and Survival Advantage of Key Cell Types in Food Allergic ChildrenKamal Ivory0Rossella Angotti1Mario Messina2Denise Bonente3Ferdinando Paternostro4Massimo Gulisano5Claudio Nicoletti6The Quadram Institute, Norwich NR4 7UQ, UKDepartment of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, ItalyDepartment of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Firenze, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50134 Firenze, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyAll allergic responses to food indicate the failure of immunological tolerance, but it is unclear why cow’s milk and egg (CME) allergies resolve more readily than reactivity to peanuts (PN). We sought to identify differences between PN and CME allergies through constitutive immune status and responses to cognate and non-cognate food antigens. Children with confirmed allergy to CME (<i>n</i> = 6) and PN (<i>n</i> = 18) and non-allergic (NA) (<i>n</i> = 8) controls were studied. Constitutive secretion of cytokines was tested in plasma and unstimulated mononuclear cell (PBMNC) cultures. Blood dendritic cell (DC) subsets were analyzed alongside changes in phenotypes and soluble molecules in allergen-stimulated MNC cultures with or without cytokine neutralization. We observed that in allergic children, constitutively high plasma levels IL-1β, IL-2, IL-4, IL-5 and IL-10 but less IL-12p70 than in non-allergic children was accompanied by the spontaneous secretion of sCD23, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12p70, IFN-γ and TNF-α in MNC cultures. Furthermore, blood DC subset counts differed in food allergy. Antigen-presenting cell phenotypic abnormalities were accompanied by higher B and T cell percentages with more Bcl-2 within CD69<sup>+</sup> subsets. Cells were generally refractory to antigenic stimulation in vitro, but IL-4 neutralization led to CD152 downregulation by CD4<sup>+</sup> T cells from PN allergic children responding to PN allergens. Canonical discriminant analyses segregated non-allergic and allergic children by their cytokine secretion patterns, revealing differences and areas of overlap between PN and CME allergies. Despite an absence of recent allergen exposure, indication of in vivo activation, in vitro responses independent of challenging antigen and the presence of unusual costimulatory molecules suggest dysregulated immunity in food allergy. Most importantly, higher Bcl-2 content within key effector cells implies survival advantage with the potential to mount abnormal responses that may give rise to the manifestations of allergy. Here, we put forward the hypothesis that the lack of apoptosis of key immune cell types might be central to the development of food allergic reactions.https://www.mdpi.com/2073-4409/12/23/2736food allergycytokinesimmunoregulationpediatric allergyapoptosis |
| spellingShingle | Kamal Ivory Rossella Angotti Mario Messina Denise Bonente Ferdinando Paternostro Massimo Gulisano Claudio Nicoletti Alteration of Immunoregulatory Patterns and Survival Advantage of Key Cell Types in Food Allergic Children Cells food allergy cytokines immunoregulation pediatric allergy apoptosis |
| title | Alteration of Immunoregulatory Patterns and Survival Advantage of Key Cell Types in Food Allergic Children |
| title_full | Alteration of Immunoregulatory Patterns and Survival Advantage of Key Cell Types in Food Allergic Children |
| title_fullStr | Alteration of Immunoregulatory Patterns and Survival Advantage of Key Cell Types in Food Allergic Children |
| title_full_unstemmed | Alteration of Immunoregulatory Patterns and Survival Advantage of Key Cell Types in Food Allergic Children |
| title_short | Alteration of Immunoregulatory Patterns and Survival Advantage of Key Cell Types in Food Allergic Children |
| title_sort | alteration of immunoregulatory patterns and survival advantage of key cell types in food allergic children |
| topic | food allergy cytokines immunoregulation pediatric allergy apoptosis |
| url | https://www.mdpi.com/2073-4409/12/23/2736 |
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