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Food allergies have been rising in prevalence since the 1990s, imposing substantial physical, psychosocial, and economic burdens on affected patients and their families. Until recently, the only therapy for food allergy was strict avoidance of the allergenic food. Recent advances in translational studies, however, have led to insights into allergic sensitization and tolerance. This article provides an overview of cutting-edge research into food allergy and immune tolerance mechanisms utilizing mouse models, human studies, and systems biology approaches. This research is being translated and implemented in the clinical setting to improve diagnosis and reduce food allergy's public health burden.

In the past decade, research in the molecular and cellular underpinnings of basic and clinical immunology has significantly advanced our understanding of allergic disorders, allowing scientists and clinicians to diagnose and treat disorders such as asthma, allergic and nonallergic rhinitis, and food allergy. In this review, we discuss several significant recent developments in basic and clinical research as well as important future research directions in allergic inflammation. Certain key regulatory cytokines, genes, and molecules have recently been shown to play key roles in allergic disorders. For example,interleukin-33 (IL-33)plays an important role in refractory disorders such as asthma, allergic rhinitis, and food allergy, mainly by inducing T helper (Th) 2 immune responses. Further, the cytokine TSLP has been shown to be a key factor in maintaining immune homeostasis and regulating inflammatory responses at mucosal barriers and targeting TSLP-mediated signaling is considered an attractive therapeutic strategy. We discuss interleukin 4 receptor pathways, which recently has shown to play a critical role among the allergic inflammatory pathways that drive allergic disorders and pathogenesis. The alarmin IL-33 has found to play a major role in type-2 immune responses in allergic diseases and clinical trials with IL33 inhibitors are underway in food allergy. Further, the cytokine Thymic Stromal Lymphopoietin (TSLP)has recently been shown a factor in maintaining immune homeostasis and regulating type-2 inflammatory responses at mucosal barriers in allergic inflammation. Also, new immune and genetic studies found that IL-4R pathways play a critical role among the allergic inflammatory pathways that drive allergic disorders and pathogenesis. In addition, new findings establish an important T cell-intrinsic role of Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) proteolytic activity in the suppression of autoimmune responses. We have seen how mutations in the filaggrin gene are significant risk factor for allergic diseases such as atopic dermatitis, asthma, allergic rhinitis, food allergy (FA), and contact allergy and hand eczema. We are only beginning to understand the mechanisms by which the human microbiota may be regulating the immune system, and how sudden changes in the composition of the microbiota may have profound effects, linked with an increased risk of developing chronic inflammatory disorders, including allergies. New research has shown the important but complex role monocytes play in such disorders as food allergies. Finally, we discuss some of the new directions of research in this area, particularly the important use of biologicals in oral immunotherapy, advances in gene therapy, multi-food therapy, novel diagnostics in diagnosing allergic disorders, and the central role that OMICS plays in creating molecular signatures and biomarkers of allergic disorders such as food allergy. Such exciting new developments and advances has significantly moved forth our ability to understand the mechanisms underlying allergic diseases for improved patient care.

Food allergies have been rising in prevalence since the 1990s, imposing substantial physical, psychosocial, and economic burdens on affected patients and their families. Until recently, the only therapy for food allergy was strict avoidance of the allergenic food. Recent advances in translational studies, however, have led to insights into allergic sensitization and tolerance. This article provides an overview of cutting-edge research into food allergy and immune tolerance mechanisms utilizing mouse models, human studies, and systems biology approaches. This research is being translated and implemented in the clinical setting to improve diagnosis and reduce food allergy's public health burden.

Objective The origin of allergic disease has traditionally been explained by IgEmediated immune responses to account for asthma, atopic dermatitis, atopic rhinitis, and food allergy. Research insights into disease origins support broader array of factors that predispose, initiate, or exacerbate altered immunity in allergic diseases: inherent epithelial barrier dysfunction, loss of immune tolerance, disturbances in gut and organ-specific microbiomes, diet, and age. Here, we discuss these influences that together form a better understanding of allergy as a systems disease. Data Sources We summarize recent advances in epithelial dysfunction, environmental influences, inflammation, infection, alterations in specific microbiome, and inherent genetic predisposition. Study Selections We performed a literature search targeting primary and review articles. Results We explored microbial-epithelial-immune interactions underlying the early-life origins of allergic disorders, and examined immune mechanisms suggesting novel disease prevention or intervention strategies. Damage to epithelial surfaces lies at the origin of various manifestations of allergic disease. As a sensor of environmental stimuli, the epithelium of the lungs, gut, and skin is impacted by an altered microbiome, air pollution, food allergens in a changed diet, and chemicals in modern detergents. This collectively leads to alterations of lung, skin, or gut epithelial surfaces, driving a type-2 immune response that underlies atopic diseases. Treatment and prevention of allergic diseases include biologics, oral desensitization, targeted gut microbiome alterations, and changes in behavior. Conclusion Understanding the spectrum of allergy as a systems disease will allow us to better define the mechanisms of allergic disorders and improve their treatment.