Abstract
BackgroundAllergy to peanuts results in severe anaphylactic responses in affected individuals, and has dramatic effects on society and public policy. Despite the health impacts of peanut-induced anaphylaxis (PIA), relatively little is known about immune mechanisms underlying the disease. Using a mouse model of PIA, we evaluated mice with deletions in four distinct immune molecules (IL7Rα, L-selectin, CD34, CD103), for perturbed responses.MethodsPIA was induced by intragastric sensitization with peanut antigen and cholera toxin adjuvant, followed by intraperitoneal challenge with crude peanut extract (CPE). Disease outcome was assessed by monitoring body temperature, clinical symptoms, and serum histamine levels. Resistant mice were evaluated for total and antigen specific serum IgE, as well as susceptibility to passive systemic anaphylaxis.ResultsPIA responses were dramatically reduced in IL7Rα−/− and L-selectin−/− mice, despite normal peanut-specific IgE production and susceptibility to passive systemic anaphylaxis. In contrast, CD34−/− and CD103−/− mice exhibited robust PIA responses, indistinguishable from wild type controls.ConclusionsLoss of L-selectin or IL7Rα function is sufficient to impair PIA, while CD34 or CD103 ablation has no effect on disease severity. More broadly, our findings suggest that future food allergy interventions should focus on disrupting sensitization to food allergens and limiting antigen-specific late-phase responses. Conversely, therapies targeting immune cell migration following antigen challenge are unlikely to have significant benefits, particularly considering the rapid kinetics of PIA.
Highlights
Food allergies affect a significant portion of the population, with direct effects on health and quality of life
We provide the first analysis of four immune molecules (IL7Rα, L-selectin, CD34, CD103) in the peanut-induced anaphylaxis (PIA) model, to determine the effect of altered adaptive responses and cell migration on food-induced anaphylaxis
Our findings demonstrate that ablation of either IL7R or L-sel dramatically reduces the severity of PIA, whereas ablation of two migrationassociated immune genes, Cd34 or Cd103, has no effect
Summary
Food allergies affect a significant portion of the population, with direct effects on health and quality of life. Peanut-specific IgE antibodies bind to FcεR on mast cells and basophils, and are cross linked by peanut antigens, resulting in rapid release of immune mediators including histamine, leukotrienes, prostaglandins and platelet-activating factor following exposure (as reviewed in [4]). These mediators contribute to a range of pathological symptoms, including increased vascular permeability (resulting in localized edema, decreased blood pressure, and rapid decrease in body temperature), diarrhea and vomiting, and fatal respiratory failure without treatment. Using a mouse model of PIA, we evaluated mice with deletions in four distinct immune molecules (IL7Rα, L-selectin, CD34, CD103), for perturbed responses
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