Mechanistic analysis of experimental food allergen-induced cutaneous reactions

Vanessa E. Prescott^*, Elizabeth Forbes^*, Paul. S. Foster^*, Klaus. Matthaei and Simon P. Hogan^*^,^,1

^* Allergy and Inflammation Research Group, Division of Molecular Bioscience,
Gene Targeting Group, The John Curtin School of Medical Research, Australian National University, Canberra; and
Division of Allergy and Immunology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, Ohio

¹Correspondence: Division of Allergy and Immunology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45220. E-mail: Simon.Hogan{at}cchmc.org

ABSTRACT

Individuals with food allergy often present with uritcaria andatopic dermatitis. Indeed, susceptibility to food allergy maypredispose to the development of these cutaneous allergic disorders.Recently, we developed a model of food allergy, whereby oralconsumption of food [pea Pisum sativum L.; expressing ${alpha}$ -amylaseinhibitor-1 ( ${alpha}$ AI) from the common bean Phaseolus vulgaris L.cv Tendergreen (pea- ${alpha}$ AI)] promotes a T helper cell type 2 (Th₂)inflammatory response and predisposes to cutaneous allergicreactions following subsequent food allergen ( ${alpha}$ AI) exposure.To delineate the kinetics of food allergen-induced cutaneousreactions and examine the inflammatory mechanisms involved inthis allergic reaction, we used interleukin (IL)-13-, IL-4 receptor ${alpha}$ -, and eotaxin-1-deficient mice and performed serum transferand CD4⁺ T cell depletion studies. We demonstrate that consumptionof pea- ${alpha}$ AI promotes an ${alpha}$ AI-specific immunoglobulin G₁ (IgG₁) andIgE antibody response. Furthermore, we show that subsequentfood allergen ( ${alpha}$ AI) challenge in the skin induced an early (3h)- and late-phase (24 h) cutaneous allergic reaction. The early-phaseresponse was associated with mast cell degranulation and thepresence of Ig, whereas the late-phase response was characterizedby a lymphoid and eosinophilic infiltrate, which was criticallyregulated by CD4⁺ T cells, IL-13, and eotaxin-1. Collectively,these studies demonstrate that food allergy can predispose tocutaneous inflammatory reactions, and these processes are criticallyregulated by Th₂immune factors.

Key Words: eosinophil • animal models • food allergy