Immunology of Food Allergy

Abstract

Many consider food allergy as the "second wave" of the allergy epidemic following the "first wave" of respiratory allergy, i.e., asthma and allergic rhinitis, plaguing westernized countries, with up to 8% of young children and 2%-3% of adults in the United States now affected by hypersensitivity reactions to various foods. In the past decade, there have been great strides in our understanding of the underlying immunopathogenesis of these disorders, which have led to improved diagnostic techniques, management strategies, and therapeutic approaches. Here we will review the most recent understanding of basic mechanisms underlying IgE-mediated food allergies and novel therapeutic approaches under investigation for both the prevention and treatment of IgE-mediated food allergies.

CD300f is a potential therapeutic target for the treatment of food allergy

“…Typically, CD103 + DCs in the small intestinal LP capture food antigens and migrate from the LP to the draining LN, where CD103 + DCs induce naïve T cells to differentiate into Tregs. 1,8 Interestingly, the percentages of CD103 + CD11b + DCs among MLN CD11c + DCs were higher in OVA-challenged WT mice after sensitization than in CD300f -/counterparts ( Figure 2J OVA/alum PBS OVA/alum OVA WT KO WT KO (n = 2) (n = 2) (n = 10) (n = 7)…”

“…It is therefore needed to identify the novel therapeutic target against food allergy. 1 We previously characterized CD300f [also known as leukocyte mono-immunoglobulin-like receptor 3 (LMIR3)] as an inhibitory receptor expressed in myeloid cells, including mast cells (MCs). The interaction between CD300f and its ligand ceramide suppresses IgEmediated mast cell activation and anaphylactic responses through phosphorylation of immunoreceptor tyrosine-based inhibitory and switch motifs.…”

“…To address this question, we used mouse models of ovalbumin (OVA)-induced IgE-and mast cell-dependent food allergy in wildtype (WT) and CD300f -/mice. 1,5 Mice were sensitized by intraperitoneal injection of OVA plus alum on days 0 and 14 and then challenged intragastrically with 25 mg OVA on days 28-38 every other day ( Figure 1A). Notably, CD300f -/mice exhibited more frequent and severe diarrhea with liquid stool than did WT mice ( Figure 1B).…”

“…According to numerous studies, Tregs inhibit both Th2 skewing, involving food antigen-specific IgE production and IL-9-mediated mast cell hyperplasia, and IgE/antigen-mediated mast cell activation, which are pivotal in the development of food allergy, whereas Th2-and mast cell-derived cytokines (eg, IL-4) downregulate Tregs. 1,6,9 Accordingly, CD300f in intestinal mast cells (possibly in concert with CD103 + CD11b + cells) inhibits the development of OVA-induced food allergy by suppressing mast cell activation with the skewing of Th2/Treg balance toward Th2. Given that the repeated administration of ceramide vesicles is effective in the treatment of food allergy, long-acting CD300f agonist drugs might be promising for preventing and/or treating food allergy.…”

Oral Immunotherapy With Egg and Milk: Changes in Peripheral Serum Cytokines Are Not Predictive Factors for Severe Adverse Reactions or for the Final Report

“…Food allergy is emerging as a "second wave" of the allergy epidemic, replacing the "first wave", which was dominated by respiratory allergy [1,2]. In the first years of life, eggs and milk are the foods that most often produce this type of reaction, which can affect up to 8% of children [3].…”