Introduction to Oral Immunity Publisher



Ziaei H ; Rezaei N
Source: Advances in Experimental Medicine and Biology Published:2026

Abstract

The oral immune system functions as a primary line of defense, composed of oral epithelial barriers, salivary antimicrobial factors, and various innate and adaptive immune components to prevent pathogen entry. Resident immune cells in oral tissues help maintain tolerance to commensal microorganisms while simultaneously responding to harmful external stimuli and contributing to systemic immune regulation. This chapter provides a comprehensive overview of the immunological components and their functions in the oral cavity, emphasizing the dual role of maintaining tolerance to commensal microbes and dietary antigens while initiating protective responses against pathogens. Any disruptions in this balance, such as oral dysbiosis or immune dysregulation, can lead to the development of local inflammatory conditions; it may also contribute to systemic immune disturbances and related pathologies. Immune mechanisms also regulate craniofacial development and postnatal bone remodeling and regeneration, mainly through cytokine-mediated signaling pathways and interactions between stem cells and immune cells. Several local and systemic immunological pathways are often dysregulated in oral inflammatory conditions, which makes them important therapeutic targets. Therapeutic strategies targeting these pathways include immune checkpoint inhibitors, microbiome-directed interventions, stem cell-based therapies, and salivary diagnostics for real-time and noninvasive immune profiling. These offer promising approaches for restoring oral and systemic immune balance. Finally, this chapter has reviewed recent technological advances, such as single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, metagenomics, and multi-omics integration, in the context of oral immunity. These novel techniques are transforming oral immunology, since they enable high-resolution characterization of cellular, microbial, and molecular interactions, and support the transition toward establishing more precise diagnosis and treatment plans. These findings suggest that oral immunity plays a critical role in linking local mucosal defense and systemic immune responses. Therefore, understanding oral immune mechanisms in health and inflammatory conditions is important for revealing disease pathogenesis and guiding targeted interventions. © 2025 Elsevier B.V., All rights reserved.