异位表达
生物
卵泡期
抗体
鼻息肉
淋巴系统
免疫学
病理
细胞生物学
医学
遗传学
基因
作者
Jia Song,Hai Wang,Zhe-Zheng Wang,Chongfeng Guo,Wei Xiang,Jingxian Li,Zhichao Wang,Jixin Zhong,Kun Huang,Robert P. Schleimer,Yin Yao,Zheng Liu
标识
DOI:10.1016/j.jaci.2023.11.913
摘要
Background
Ectopic lymphoid tissues (eLTs) and associated follicular helper T (TFH) cells contribute to local immunoglobulin hyperproduction in nasal polyps (NPs). Follicular regulatory T (TFR) cells in secondary lymphoid organs counteract TFH cells and suppress immunoglobulin production; however, the presence and function of TFR cells in eLTs in peripheral diseased tissues remain poorly understood. Objective
We sought to investigate the presence, phenotype, and function of TFR cells in NPs. Methods
The presence, abundance, and phenotype of TFR 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
TFR cells were primarily localized within eLTs in NPs. TFR cell frequency and TFR cell/TFH cell ratio were decreased in NPs with eLTs compared with NPs without eLTs and control inferior turbinate tissues. TFR cells displayed an overlapping phenotype with TFH cells and FOXP3+ regulatory T cells in NPs. Polyp TFR cells had reduced CTLA-4 expression and decreased capacity to inhibit TFH cell–induced immunoglobulin production compared with their counterpart in blood and tonsils. Blocking CTLA-4 abolished the suppressive effect of TFR cells. Lower vitamin D receptor expression was observed on polyp TFR cells compared with TFR cells in blood and tonsils. Vitamin D treatment upregulated CTLA-4 expression on polyp TFR cells and restored their suppressive function in vitro. Conclusions
Polyp TFR cells in eLTs have decreased CLTA-4 and vitamin D receptor expression and impaired capacity to suppress TFH cell–induced immunoglobulin production, which can be reversed by vitamin D treatment in vitro.
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