Nasal IL-4+CXCR5+CD4+ T follicular helper cell counts correlate with local IgE production in eosinophilic nasal polyps

Background: Locally produced IgE contributes to the initiation and development of eosinophilic inflammation in eosinophilic nasal polyps independent of systemic atopy. However, whether CXCR5(+)CD4(+) T follicular helper (T-FH) cells are involved in local IgE production at mucosal sites remains unexplored. Objective: We sought to explore the presence, phenotype, and function of CXCR5(+)CD4(+) T-FH cells in eosinophilic nasal polyp tissues compared with noneosinophilic nasal polyp and control normal nasal tissues. Methods: T-FH cell-surface phenotypes and subsets and B-cell subsets in nasal tissues and peripheral blood were studied by means of flow cytometry. Immunohistochemistry was used to detect the tissue location of T-FH cells. Sorted nasal T-FH cells and CXCR5(-) T cells were cultured with autologous naive B cells purified from blood. Results: Nasal T-FH cells expressed inducible costimulator, programmed cell death protein 1, and the transcription factor B-cell lymphoma 6 (Bcl-6) at an intermediate level when compared with bona fide T-FH cells in tonsils and circulating T-FH cells. Although counts of total T-FH cells and IL-21(+), IFN-gamma(+), and IL-17(+) T-FH cells were increased in both eosinophilic and noneosinophilic nasal polyp tissues compared with those in normal nasal tissues, IL-4(+) T-FH cell counts were only increased in eosinophilic polyp tissues. IL-4 and IL-21 were involved in polyp T-FH cell-induced IgE production from naive B cells, and nasal IL-4(+) T-FH cell counts correlated highly with local IgE levels in vivo. IL-4(+)Bcl-6(+)CD4(+) T-FH cells were identified in ectopic lymphoid structures in eosinophilic nasal polyps. T-FH cells also positively correlated with germinal center B cells and plasma cells in nasal tissues. Conclusion: Nasal IL-4(+) T-FH cells might be involved in local IgE production in eosinophilic nasal polyps.