<div>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 IL-17A, CXCL13 and lymphotoxin (LT) in
eLT 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+ ﬁbroblastic reticular cell (FRC) type, 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 LTα1β2 in NPs with eLTs. CXCL13 upregulated LTα1β2
expression on polyp B cells, which in turn promoted CXCL13 production
from polyp B cells and nasal stromal cells. LTα1β2 induced expansion of
FRCs and CD31+Pdpn+ lymphoid endothelial cells, corresponding to the
phenotypic characteristic of stromal cells in NPs with eLTs. IL-17A gene
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 LTα1β2 in the enlargement of
eLTs in NPs.</div>