Oral tolerance can develop after frequent exposure to food allergens. Upon ingestion, food is digested into small protein fragments in the gastrointestinal tract. Small food particles are later absorbed into the human body. Interestingly, some of these ingested food proteins can cause allergic immune responses, which can lead to food allergy. So far it has not been completely elucidated how these proteins become immunogenic and cause food allergies. In contrast, oral tolerance helps to prevent the pathologic reactions against different types of food antigens from animal or plant origin. Tolerance to food is mainly acquired by dendritic cells, epithelial cells in the gut, and the gut microbiome. A subset of CD103+ DCs is capable of inducing T regulatory cells (Treg cells) that express anti-inflammatory cytokines. Anergic T cells also contribute to oral tolerance, by reducing the number of effector cells. Similar to Treg cells, B regulatory cells (Breg cells) suppress effector T cells and contribute to the immune tolerance to food allergens. Furthermore, the human microbiome is an essential mediator in the induction of oral tolerance or food allergy. In this review, we outline the current understanding of regulatory immune mechanisms in oral tolerance. The biological changes reflecting early consequences of immune stimulation with food allergens should provide useful information for the development of novel therapeutic treatments.
CONCLUSION
Loss of oral tolerance can lead to the development of food allergy in children and adults. However, the development of food allergy in terms of molecular and cellular mechanisms has not yet been demonstrated. The induction or loss of oral tolerance is likely modulated by the combination of DCs, Treg cells, Breg cells, and microbiome. DCs are capable of inducing Treg cells, which produce anti-inflammatory cytokines and are able to suppress T effector cells. Additionally, Breg cells can produce antiinflammatory cytokines as well and can produce IgG4, which is the anti-inflammatory Ig isotype. So far food allergies are mainly managed by strict avoidance of the food allergens and can only be treated with immunotherapy. How immunotherapy exactly works is not entirely understood. Therefore, the underlying mechanisms of induction and loss of oral tolerance need to be more clearly identified so novel therapeutic treatments can be developed.
