Early life factors that affect allergy development

The recent rise in the incidence of allergic disease suggests that changing environmental factors can influence the risk of allergic sensitization. Environmental exposures that occur during the first few months of life can influence the risk of allergy development in later childhood.The timing of the first exposure to potential allergens, as well as the route of the first exposure, can influence whether tolerance or allergic sensitization occurs. Cutaneous antigen exposure predisposes towards a T helper 2 (TH2) cell-skewing environment, which leads to allergic sensitization, whereas oral antigen exposure predisposes towards tolerogenic responses that are mediated by retinal dehydrogenase 2 (RALDH2)-expressing CD103+ dendritic cells.Exposure to microbial endotoxins alongside potential allergens can protect against allergic sensitization through the stimulation of innate pattern recognition receptors.Many of the environmental factors that are associated with allergy development modify the composition and diversity of the microbiota. Recent studies have demonstrated that the microbiota composition in the first few months of life can be predictive of allergy development in later childhood, and studies in mice have demonstrated that the absence of key bacterial microbiota species can be a driving factor in allergy development.Infection with pathogens can protect against allergic sensitization by promoting tolerogenic responses or can exacerbate existing disease by promoting the release of TH2 cell-skewing cytokines. Fungal infections and certain bacterial and viral species are associated with the exacerbation of existing allergies, whereas helminth species and certain bacterial and viral species are associated with protection against allergic sensitization.It is clear that there are notable differences in the quality of immune responses to foreign antigens and stimuli even in the few weeks after birth in mice; how this developmental time window translates into the setting of human neonates is not yet clear. Both microorganism-derived and helminth-derived molecules have great potential for therapeutic and prophylactic use in infants who are at a high risk of developing allergies.