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Stromal cells and B cells orchestrate ectopic lymphoid tissue formation in nasal polyps
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  • 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,
  • Pei-Song Gao,
  • Zheng Liu
Zhe-Zheng Wang
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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Jia Song
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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Hai Wang
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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Jing-Xian Li
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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Qiao Xiao
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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Ze Yu
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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Zhi-Chao Wang
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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Jin-Xin Liu
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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Li Pan
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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Yin Yao
Huazhong University of Science and Technology
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Cai-Ling Chen
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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Xiang Lu
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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Chaohong Liu
School of Basic Medicine, Huazhong University of Science and Technology
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Pei-Song Gao
Johns Hopkins University
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Zheng Liu
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
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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 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.

Peer review status:ACCEPTED

09 May 2020Submitted to Allergy
09 May 2020Submission Checks Completed
09 May 2020Assigned to Editor
11 May 2020Reviewer(s) Assigned
01 Jun 2020Review(s) Completed, Editorial Evaluation Pending
01 Jun 2020Editorial Decision: Revise Minor
06 Sep 20201st Revision Received
07 Sep 2020Submission Checks Completed
07 Sep 2020Assigned to Editor
08 Sep 2020Reviewer(s) Assigned
22 Sep 2020Review(s) Completed, Editorial Evaluation Pending
23 Sep 2020Editorial Decision: Accept