Abstract
Background: 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.Methods: 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.Results: 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.Conclusions: 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.
Original language | English |
---|---|
Article number | 15 |
Journal | Allergy, Asthma and Clinical Immunology |
Volume | 8 |
Issue number | 1 |
DOIs | |
Publication status | Published - Aug 31 2012 |
Bibliographical note
Funding Information:We are grateful to Takahide Murakami for genotyping, Hermann J. Ziltener for providing IL7R−/− and Lsel−/− mice, Helen Merkens and Kimberley Allan for technical support, and the BRC Animal Care Facility for animal handling. This work was funded by grants from the Canadian Group on Food Allergy Research (CanGoFar; Grant #07B1), the AllerGen Network NCE and the Canadian Institutes of Health Research (CIHR; MOP-84545). SM was supported through a CIHR and Heart and Stroke Foundation of Canada Fellowship from the Centre for Blood Research (CBR), JB was supported by the Multiple Sclerosis Society of Canada, EJD was supported through a NSERC Postgraduate Scholarship and a UBC 4-Year Fellowship and MJG holds a fellowship from the CIHR/Michael Smith Foundation for Health Research (MSFHR) Transplantation Training Program. KMM is a MSFHR Scholar (Senior) and CBR Member.
ASJC Scopus Subject Areas
- Immunology and Allergy
- Immunology
- Pulmonary and Respiratory Medicine
PubMed: MeSH publication types
- Journal Article