Understanding food allergy through neuroimmune interactions in the gastrointestinal tract

Food allergies are adverse immune reactions to food proteins in the absence of oral tolerance, and the incidence of allergies to food, including peanut, cow's milk, and shellfish, has been increasing globally. Although advancements have been made toward understanding the contributions of the type 2 immune response to allergic sensitization, crosstalk between these immune cells and neurons of the enteric nervous system is an area of emerging interest in the pathophysiology of food allergy, given the close proximity of neuronal cells of the enteric nervous system and type 2 effector cells, including eosinophils and mast cells. At mucosal sites, such as the gastrointestinal tract, neuroimmune interactions contribute to the sensing and response to danger signals from the epithelial barrier. This communication is bidirectional, as immune cells express receptors for neuropeptides and transmitters, and neurons express cytokine receptors, allowing for the detection of and response to inflammatory insults. In addition, it seems that neuromodulation of immune cells including mast cells, eosinophils, and innate lymphoid cells is critical for amplification of the type 2 allergic immune response. As such, neuroimmune interactions may be critical targets for future food allergy therapies. This review evaluates the contributions of local enteric neuroimmune interactions to the underlying immune response in food allergy and discusses considerations for future investigations into targeting neuroimmune pathways for treatment of food allergies.