The mucosal immune microenvironment in chronic pharyngitis: epithelial barrier dysfunction, inflammatory persistence, and therapeutic perspectives

Chronic pharyngitis is a clinically heterogeneous condition in which persistent throat symptoms, visible mucosal abnormalities, and underlying biological processes do not necessarily coincide. This critical narrative review synthesizes evidence from human chronic pharyngitis, experimental injury models, adjacent upper-airway disorders, and other mucosal systems to examine how epithelial barrier function, innate and adaptive immunity, microbial ecology, sensory signaling, and tissue repair may contribute to disease persistence. Experimental studies identify epithelial injury and activation of shared inflammatory and stress-response pathways, while human observations highlight substantial variation in anatomical site, microbial findings, immune organization, and treatment response. Adaptive immune responses appear strongly context dependent; microbial community changes are most informative when linked to organism viability, metabolite production, host sensing, or colonization resistance; and sensory pathways may contribute to symptoms partly independently of measurable inflammation. We propose that persistent disease can arise through three overlapping routes: continued exposure, durable alteration of tissue responsiveness, and incomplete resolution or repair, with microbial and sensory processes acting as modifiers. This framework separates symptom improvement, biological target engagement, and durable restoration of tissue function as distinct therapeutic outcomes. Future studies should prioritize anatomically precise longitudinal cohorts, site-resolved single-cell and spatial profiling, functional perturbation in primary pharyngeal systems, and mechanism-informed trials with follow-up after treatment withdrawal. By linking clinical presentation to local biological function and recovery trajectories, chronic pharyngitis may be reclassified into reproducible biological subgroups that support more precise mechanistic investigation and treatment.