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Stromal cells and B cells orchestrate ectopic lymphoid tissue formation in nasal polyps
Author(s) -
Wang ZheZheng,
Song Jia,
Wang Hai,
Li JingXian,
Xiao Qiao,
Yu Ze,
Wang ZhiChao,
Liu JinXin,
Pan Li,
Yao Yin,
Chen CaiLing,
Lu Xiang,
Liu Chaohong,
Gao Peisong,
Liu Zheng
Publication year - 2021
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.14612
Subject(s) - cxcl13 , stromal cell , flow cytometry , chemokine , immunology , biology , chemistry , microbiology and biotechnology , pathology , cancer research , inflammation , medicine , chemokine receptor
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 LTα 1 β 2 in NPs with eLTs. CXCL13 upregulated LTα 1 β 2 expression on B cells, which in turn promoted CXCL13 production in nasal B cells and stromal cells. LTα 1 β 2 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 LTα 1 β 2 in the enlargement of eLTs in NPs.