Research Article: IL-7Rα and L-selectin, but not CD103 or CD34, are required for murine peanut-induced anaphylaxis

Date Published: August 31, 2012

Publisher: BioMed Central

Author(s): Steven Maltby, Erin J DeBruin, Jami Bennett, Matthew J Gold, Matthew C Tunis, Zhiqi Jian, Jean S Marshall, Kelly M McNagny.


Allergy 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.

PIA 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.

PIA 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.

Loss 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.

Partial Text

Food allergies affect a significant portion of the population, with direct effects on health and quality of life. Of all food sensitivities, peanut allergies account for the most fatalities
[1] and exposure to peanut antigen in affected individuals results in severe, rapid, systemic anaphylactic responses. Despite the severity of peanut anaphylactic responses, few effective treatments or therapies exist and most focus on limiting allergen exposure and management of symptoms. While peanut allergy prevalence is relatively low (estimated ~1-2% of the total population), the consequences of exposure are high and the effects of peanut allergy are disproportionately large in society

Peanut-induced anaphylaxis is a severe medical condition, with major effects on individual patient health and social policy. Despite this, we lack a basic understanding of unique underlying mechanisms of the disease. Recent studies using a mouse model of PIA have highlighted the role of B cells in peanut allergy development or focussed on potential therapeutic interventions
[5-7]. However, the importance of other specific immune molecules and immune processes underlying this disease are not well understood. In the current study, we used a series of knockout mice to survey the importance of cytokine receptors and adhesion/trafficking molecules in susceptibility to food allergy with the goal of identifying novel pathways as points of therapeutic intervention.

No conflict of interest is declared by any authors of this manuscript.

SM and JB designed and performed all experiments and wrote the manuscript. EDB coordinated reagent procurement and initiation of the project, participated in experiment harvests and edited the manuscript. MJG, MCT, and ZJ performed selected assays and edited the manuscript. JSM and KMM supervised trainees, edited the manuscript, and provided reagents. All authors read and approved the final manuscript.




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