The role of regulatory T cells in the acquisition of tolerance to food allergens in children

Abstract

Food allergy is a pathological immune reaction that identifies certain harmless food proteins, usually tolerated by the majority of the people, as a threat. The prevalence of these food allergies is increasing worldwide and currently affects 8% of children. Exacerbated reactions to milk, egg and peanut are the most frequent in the pediatric population. It is well known that allergic diseases are a type 2 T-helper (Th2) immune response, characterized by the elevated production of IgE antibodies. However, little is known about the immune mechanisms responsible for the development of clinical tolerance toward food allergens. Recent studies have suggested the key role of regulatory T cells (Tregs) in controlling allergic inflammation. In this review, we discuss the importance of Tregs in the pathogenesis of food allergy and the acquisition of oral tolerance in children. Further investigation in this area will be crucial for the identification of predictive markers and the development of new therapies, which will represent a clinical and social benefit for these allergic diseases.

The clinical and immunological basis of early food introduction in food allergy prevention

“…Regulatory B (Breg) cells are immunosuppressive B cells, characterized by the production of IL-10, IL-35 and transforming growth factor beta (TGF-β). IL-10 secreting Breg (Br1) cells, are known for being the main producers of IgG4 ( 49 ). Through the secretion of IL-10, IL-35 and TGF-β, Breg cells are known to suppress the activation and proliferation of effector T cells, and also induce the differentiation of FoxP3 + regulatory T cells and type 1 regulatory (Tr1) cells ( Figure 1 ).…”

“…Furthermore, they suppress eosinophils, mast cells and basophils. Inducible Treg cells can be subdivided into three subsets: induced FoxP3 + Treg cells, Tr1 cells and T helper 3 cells (Th3 cells) ( 49 ). FoxP3 + Treg cells express CCR6 and have the capacity to produce IL-17 upon activation.…”

“…The Treg cell count was similar or even higher in infants compared to adolescents and adults, given their involvement in maternal-fetal tolerance. The immaturity and plasticity of the immune system, together with the maintained thymic functionality in children, could be decisive in both the onset of FA and the acquisition of tolerance to allergens ( 49 ). Treg cells can control the sensitization and effector phases of allergic reactions through multiple suppression mechanisms and both Treg cell deficiency and Treg cell dysfunction have been described in the process of allergy development ( 49 , 52 ).…”

“…The immaturity and plasticity of the immune system, together with the maintained thymic functionality in children, could be decisive in both the onset of FA and the acquisition of tolerance to allergens ( 49 ). Treg cells can control the sensitization and effector phases of allergic reactions through multiple suppression mechanisms and both Treg cell deficiency and Treg cell dysfunction have been described in the process of allergy development ( 49 , 52 ). Akdis et al showed that higher frequencies of allergen-specific Treg cells were encountered in healthy patients and that Treg cells isolated from the blood of house dust mite or birch pollen allergic patients were less functional than Treg cells isolated from healthy subjects ( 53 ).…”

“…Akdis et al showed that higher frequencies of allergen-specific Treg cells were encountered in healthy patients and that Treg cells isolated from the blood of house dust mite or birch pollen allergic patients were less functional than Treg cells isolated from healthy subjects ( 53 ). Likewise in food allergy, the state of allergen sensitization can be associated with depletion of Treg cells following hen’s egg, cow’s milk or peanut exposure and the impaired capacity to regenerate the Treg pool is an important factor to determine clinical allergy versus a sensitized but tolerant state ( 49 , 52 ).…”