Tissue-resident memory T cells in the nasal mucosa: gatekeepers of chronicity and relapse in allergic rhinitis.

Allergic rhinitis (AR) is a pervasive type-2 inflammatory disorder of the nasal mucosa whose clinical course is defined less by acute flares than by recurrence and apparent resistance to cure. Although AR has traditionally been framed as a systemic, IgE-driven disease, a growing body of evidence points to the nasal mucosa itself as a site of durable, antigen-specific immune memory. Tissue-resident memory T (TRM) cells - non-recirculating, longevity-endowed lymphocytes that lodge in barrier tissues - are ideally positioned to convert transient allergen exposure into persistent inflammation. This mini review synthesizes human and preclinical evidence that nasal TRM cells, including Th2-polarized CD4+ subsets and a recently described pathogenic CD8+ subset (first characterized in recurrent chronic rhinosinusitis with nasal polyps, CRSwNP), constitute a credible - but still largely hypothetical - cellular substrate for AR chronicity and post-immunotherapy relapse. We propose that the 2025 discovery of granzyme K (GZMK)-expressing CD8+ memory T cells driving recurrent airway inflammation (Lan et al., Nature 2025) provides a translatable framework for understanding AR relapse. We note that direct, high-resolution human evidence for nasal TRM in pure AR remains limited; accordingly, we integrate findings from CRSwNP, lower-airway disease, and animal models as a translatable evidence base and explicitly flag where each conclusion is established versus hypothetical. We outline how targeting TRM retention, phenotype, or effector molecules could complement allergen immunotherapy.