A Role Of Stromal Cells And B Cells In Ectopic Lymphoid Tissue Formation In Nasal Polyps

Background:Although the importance of ectopic lymphoid tissues（e LTs）in the pathophysiology of nasal polyps（NPs）is increasingly appreciated,the mechanisms underlying their formation remain unclear.Objective:To study the role of IL-17A,CXCL13 and lymphotoxin（LT）in e LT formation in NPs.Methods:The expression of CXCL13 and LT as well as their receptors,and the phenotypes of stromal cells in NPs were studied by flow cytometry,immunostaining,and RT-PCR.Purified nasal stromal cells and polyp B cells were cultured and a murine model with nasal type 17 inflammation was established for the mechanistic study.Results:Excessive CXCL13 production was found in NPs and correlated with enhanced IL-17A expression.Stromal cells,with an expansion of CD31^-Pdpn⁺fiber reticular cell（FRC）type,were the major source of CXCL13 in NPs without e LTs.IL-17A induced FRC expansion and CXCL13 production in nasal stromal cells.Nevertheless,B cells were the main source of CXCL13 and LTα₁β₂ in NPs with e LTs.CXCL13 upregulated LTα₁β₂expression on B cells,which in turn promoted CXCL13 production from nasal B and stromal cells.LTα₁β₂ induced expansion of FRCs and CD31⁺Pdpn⁺lymphoid endothelial cells,corresponding to the phenotypic characteristic of stromal cells in NPs with e LTs.IL-17A gene knockout,and CXCL13 and LTβR blockage diminished nasal e LT formation in the murine model.Conclusion:For the first time,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 LTα₁β₂ in the enlargement of e LTs in NPs.