Phenotypic Analysis of Nasal CD69+ CD4+ Tissue-Resident Memory T Cells in Eosinophilic Chronic Rhinosinusitis With Nasal Polyps

Abstract

Background and Objectives: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease, classified into eosinophilic and non-eosinophilic subtypes. Although CD4+ tissue-resident memory T (T<inf>RM</inf>) cells play diverse roles in tissue homeostasis, their phenotypic and functional characteristics in the nasal tissue of patients with eosinophilic CRS (ECRS) remain poorly defined. Methods: Nasal polyp tissue and/or peripheral blood (PB) samples were obtained from patients with ECRS undergoing endoscopic sinus surgery. The phenotypes and functions of nasal CD69+ CD4+ T cells were analyzed using flow cytometry. Results: The frequency of CD69+CD103– cells among nasal CD4+ T cells was significantly higher in patients with ECRS compared to controls. Analysis of paired PB and nasal tissue samples from ECRS patients revealed that CD69+CD103– CD4+ T cells were almost exclusively present in nasal tissues and exhibited tissue-resident phenotypes, marked by high expression of CD49a and CXCR6. In ECRS, these nasal CD69+CD103– CD4+ T cells expressed high levels of T helper 2 (Th2) cell markers, including CRTH2 and GATA3. Consistently, these T cells demonstrated a robust capacity to produce IL-4 and IL-5. These findings were corroborated by analyses of publicly available single-cell RNA sequencing datasets. Furthermore, the frequency of nasal CD69+CD103– CD4+ T cells was significantly associated with higher Lund-Mackay CT scores and reduced olfactory function in patients with ECRS. Conclusion: The current investigation demonstrates that nasal CD69+CD103– CD4+ T<inf>RM</inf> cells include a high frequency of Th2 cells and are associated with severe disease. © 2025 Korean Rhinologic Society.