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-γ⁺, 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.