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

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease, classified into eosinophilic and non-eosinophilic subtypes. Although CD4+ tissue-resident memory T (TRM) 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+ TRM cells include a high frequency of Th2 cells and are associated with severe disease.