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Background: Ectopic lymphoid tissues (eLTs) and associated follicular helper T (T FH ) cells contribute to local immunoglobulin hyperproduction in nasal polyps (NPs). Follicular regulatory T (T FR ) cells in secondary lymphoid organs counteract T FH cells and suppress immunoglobulin production; however, the presence and function of T FR cells in eLTs in peripheral diseased tissues remain poorly understood., Objective: We sought to investigate the presence, phenotype, and function of T FR cells in NPs., Methods: The presence, abundance, and phenotype of T FR cells in NPs were examined using single-cell RNA sequencing, immunofluorescence staining, and flow cytometry. Sorted polyp and circulating T-cell subsets were cocultured with autologous circulating naïve B cells, and cytokine and immunoglobulin production were measured by ELISA., Results: T FR cells were primarily localized within eLTs in NPs. T FR cell frequency and T FR cell/T FH cell ratio were decreased in NPs with eLTs compared with NPs without eLTs and control inferior turbinate tissues. T FR cells displayed an overlapping phenotype with T FH cells and FOXP3 + regulatory T cells in NPs. Polyp T FR cells had reduced CTLA-4 expression and decreased capacity to inhibit T FH cell-induced immunoglobulin production compared with their counterpart in blood and tonsils. Blocking CTLA-4 abolished the suppressive effect of T FR cells. Lower vitamin D receptor expression was observed on polyp T FR cells compared with T FR cells in blood and tonsils. Vitamin D treatment upregulated CTLA-4 expression on polyp T FR cells and restored their suppressive function in vitro., Conclusions: Polyp T FR cells in eLTs have decreased CLTA-4 and vitamin D receptor expression and impaired capacity to suppress T FH cell-induced immunoglobulin production, which can be reversed by vitamin D treatment in vitro., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear., Objective: We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP., Methods: We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cμ and Iε-Cγ circle transcripts was detected by using seminested PCR., Results: Increased formation of eLTs with germinal center-like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cμ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps., Conclusion: eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)