Immunopathology of Oral Allergies: Mechanisms and Therapeutic Innovations

Oral allergic diseases, including oral allergy syndrome, allergic contact stomatitis, and lichenoid reactions, represent complex immune-mediated conditions that extend beyond localised mucosal inflammation. Emerging evidence suggests that oral allergic responses may influence systemic immune homeostasis through multiple pathways, including the oral-gut axis, dissemination of inflammatory mediators, and potential trafficking of activated immune cells. The oral cavity serves as a critical interface where allergen exposure triggers both local Type I and Type IV hypersensitivity reactions that can propagate systemically. Dysregulated oral immune responses may contribute to systemic allergic conditions, while systemic inflammatory states can reciprocally exacerbate oral allergic manifestations. Despite growing recognition of bidirectional oral-systemic immunological crosstalk, the mechanistic pathways linking oral allergic immunopathology to systemic health outcomes remain poorly characterised. Understanding these causal relationships is essential for developing targeted therapeutic interventions that address both oral and systemic manifestations of allergic disease.

This Research Topic aims to elucidate the mechanistic relationships between oral allergic immunopathology and systemic immune function, addressing critical gaps in understanding how localised oral hypersensitivity reactions influence broader physiological systems. Specifically, we seek to investigate: (1) causal pathways through which oral allergic immune responses affect systemic organs via inflammatory mediator dissemination, immune cell migration, and neuroimmune signaling; (2) mechanisms by which oral dysbiosis and allergen-induced microbiome perturbations modulate systemic immune responses through the oral-gut axis; (3) bidirectional interactions whereby systemic inflammatory conditions (e.g., atopic diseases, autoimmune disorders) alter oral mucosal immune surveillance and allergic susceptibility; (4) the role of trained immunity and immune priming in oral allergen exposure as determinants of systemic allergic phenotypes.

Recent advances in single-cell immunophenotyping, spatial transcriptomics, and longitudinal microbiome analysis now enable detailed mechanistic dissection of these relationships. Furthermore, emerging immunotherapeutic approaches, including sublingual immunotherapy and targeted biologics, have the potential to modulate both oral and systemic allergic responses. This Research Topic will compile review articles as well as mechanistic studies employing in vitro models, animal experimentation, and translational human research that establish causal rather than correlative links between oral allergic immunopathology and systemic health outcomes.

We welcome mechanistic studies that establish causal relationships between oral allergic immunopathology and systemic health. Contributions should address specific themes, including:

• Mechanistic pathways of oral-systemic immune crosstalk: Studies identifying how oral allergic responses trigger systemic immune activation through inflammatory mediator release, immune cell trafficking, or neuroimmune mechanisms.
• Oral-gut axis in allergic disease: Research defining causal relationships between oral allergen exposure, microbiome alterations, and systemic immune dysregulation using gnotobiotic models, microbial transfer experiments, or longitudinal human cohorts.
• Bidirectional oral-systemic interactions: Investigations of how systemic allergic or inflammatory conditions reciprocally influence oral immune responses and allergic susceptibility.
• Therapeutic interventions with dual effects: Studies evaluating treatments (immunotherapy, biologics, microbiome modulation) that simultaneously address oral and systemic allergic manifestations.
• Biomarkers and diagnostic tools: Development of markers indicating oral-systemic immune crosstalk in allergic disease.

Correlative studies without mechanistic insight fall outside this scope.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Community Case Study
• Curriculum, Instruction, and Pedagogy
• Data Report
• Editorial
• FAIR² Data
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Community Case Study
• Curriculum, Instruction, and Pedagogy
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Policy Brief
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Oral Immunology, Allergic Conditions, Oral Allergies, Immune Responses in Oral Cavity, Oral Microbiota, Oral Dysbiosis.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.