Gut mucosal immune responses - Implications for celiac disease and food allergy

The intestinal mucosa employs a diverse set of defense mechanisms-from mucosal barrier regulation to immunoregulatory pathways-to maintain homeostasis despite constant exposure to microbial and dietary antigens. Failure to establish immune tolerance to food antigens can lead to pathological conditions such as celiac disease (CeD) and food allergies. This review provides an overview of the sequential processes that support tolerance to food antigens and examines how gene-environment interactions contribute to the pathogenesis of CeD and food allergies. Although the exact nature of the environmental triggers is unknown, microbial agents - whether bacterial or viral- are believed to play a critical role in disrupting homeostatic mechanisms in genetically predisposed individuals. Tolerogenic responses to dietary antigens can be compromised by environmentally induced local inflammation or epithelial barrier disruption, leading to the expansion of T helper 1 (T_H1) responses in CeD and T_H2 responses in food allergies. This divergence in immune activation across distinct mucosal sites underscores the unique immunopathogenesis of CeD and food allergies-conditions for which our understanding has grown significantly, yet effective interventions remain limited.