Stromal cells and B cells orchestrate ectopic lymphoid tissue formation in nasal polyps.
Allergy
; 76(5): 1416-1431, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33022771
ABSTRACT
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 ß2 in NPs with eLTs. CXCL13 upregulated LTα1 ß2 expression on B cells, which in turn promoted CXCL13 production in nasal B cells and stromal cells. LTα1 ß2 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 LTßR 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 ß2 in the enlargement of eLTs in NPs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pólipos Nasais
/
Estruturas Linfoides Terciárias
Limite:
Animals
Idioma:
En
Revista:
Allergy
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China