Stromal cells and B cells orchestrate ectopic lymphoid tissue formation in nasal polyps

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作者：Zhe-Zheng Wang, Jia Song, Hai Wang, Jing-Xian Li, Qiao Xiao, Ze Yu, Zhi-Chao Wang, Jin-Xin Liu, Li Pan, Yin Yao, Cai-Ling Chen, Xiang Lu, Chaohong Liu, Peisong Gao, Zheng Liu
期刊：ALLERGY
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Background:Although the importance of ectopic lymphoid tissues (eLTs) in the pathophysiology of nasal polyps (NPs) is increasingly appreciated, the mechanisms underlying their formation remain unclear.

Objective:To study the role of interleukin (IL)-17A, C-X-C motif chemokine ligand 13 (CXCL13) and lymphotoxin (LT) in eLT formation in NPs.

Methods:The expression levels of CXCL13 and LT and their receptors, in addition to the phenotypes of stromal cells in NPs, were studied by flow cytometry, immunostaining, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Purified nasal stromal cells and B cells were cultured, and a murine model of nasal type 17 inflammation was established by intranasal curdlan challenge for the mechanistic study.

Results:The excessive CXCL13 production in NPs correlated with enhanced IL-17A expression. Stromal cells, with CD31^- Pdpn⁺ fibroblastic reticular cell (FRC) expansion, were the major source of CXCL13 in NPs without eLTs. IL-17A induced FRC expansion and CXCL13 production in nasal stromal cells. In contrast, B cells were the main source of CXCL13 and LTα₁ β₂ in NPs with eLTs. CXCL13 upregulated LTα₁ β₂ expression on B cells, which in turn promoted CXCL13 production in nasal B cells and stromal cells. LTα₁ β₂ induced expansion of FRCs and CD31⁺ Pdpn⁺ lymphoid endothelial cells, which were the predominant stromal cell types in NPs with eLTs. IL-17A knockout and CXCL13 and LTβR blockage diminished nasal eLT formation in the murine model.

Conclusion:We identified an important role of IL-17A-induced stromal cell remodeling in the initiation and crosstalk between B and stromal cells via CXCL13 and LTα₁ β₂ in the enlargement of eLTs in NPs.