Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Παρασκευή 16 Φεβρουαρίου 2018

Mechanism for Initiation of Food Allergy: Dependence on skin barrier mutations and environmental allergen co-stimulation

Publication date: Available online 15 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Matthew Walker, Jeremy Green, Ryan Ferrie, Ashley Queener, Mark H. Kaplan, Joan M. Cook-Mills
BackgroundMechanisms for the development of food allergy in neonates are unknown but are clearly linked in patient populations to a genetic predisposition towards skin barrier defects. Whether skin barrier defects functionally contribute to development of food allergy is unknown.ObjectiveThe purpose of the study was to determine whether skin barrier mutations, that are primarily heterozygous in patient populations, contribute to the development of food allergy.MethodsMice heterozygous for the Flgft and Tmem79ma mutations were skin sensitized with environmental allergens and food allergens. After sensitization, mice received oral challenge with food allergen and then inflammation, inflammatory mediators, and anaphylaxis were measured.ResultsWe define development of inflammation, inflammatory mediators, and food allergen-induced anaphylaxis in neonatal mice with skin barrier mutations following brief concurrent cutaneous exposure to food and environmental allergens. Moreover, neonates of allergic mothers have elevated responses to suboptimal sensitization with food allergens. Importantly, the responses to food allergens by these neonatal mice were dependent on genetic defects in skin barrier function and on exposure to environmental allergens. Blockade of ST2 during skin sensitization inhibited development of anaphylaxis, antigen-specific IgE and inflammatory mediators. The neonatal anaphylactic responses and antigen-specific IgE were also inhibited by oral pre-exposure to food allergen but, interestingly, this was blunted by concurrent pre-exposure of the skin to environmental allergen.ConclusionThese studies uncover mechanisms for food allergy sensitization and anaphylaxis in neonatal mice that are consistent with features of human early life exposures and genetics in clinical food allergy and demonstrate that changes in barrier function drive development of anaphylaxis to food allergen.



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