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

Abstract

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.

The authors' abstract, as published at the source. Frontiers in Immunology, 2026 · DOI ↗