Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps

Jia Song; Hai Wang; Ya Na Zhang; Ping Ping Cao; Bo Liao; Zhe Zheng Wang; Li Li Shi; Yin Yao; Guan Ting Zhai; Zhi Chao Wang; Li Meng Liu; Ming Zeng; Xiang Lu; Heng Wang; Xiang Ping Yang; Di Yu; Claus Bachert; Zheng Liu

doi:10.1016/j.jaci.2017.10.014

Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps

Jia Song, Hai Wang, Ya Na Zhang, Ping Ping Cao, Bo Liao, Zhe Zheng Wang, Li Li Shi, Yin Yao, Guan Ting Zhai, Zhi Chao Wang, Li Meng Liu, Ming Zeng, Xiang Lu, Heng Wang, Xiang Ping Yang, Di Yu, Claus Bachert, Zheng Liu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

Abstract

Background: The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. Objective: We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP. Methods: We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cμ and Iε-Cγ circle transcripts was detected by using seminested PCR. Results: Increased formation of eLTs with germinal center–like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cμ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps. Conclusion: eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP.

Original language	English
Pages (from-to)	927-937
Number of pages	11
Journal	Journal of Allergy and Clinical Immunology
Volume	141
Issue number	3
DOIs	https://doi.org/10.1016/j.jaci.2017.10.014
Publication status	Published - Mar 2018

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10.1016/j.jaci.2017.10.014

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Song, J., Wang, H., Zhang, Y. N., Cao, P. P., Liao, B., Wang, Z. Z., Shi, L. L., Yao, Y., Zhai, G. T., Wang, Z. C., Liu, L. M., Zeng, M., Lu, X., Wang, H., Yang, X. P., Yu, D., Bachert, C., & Liu, Z. (2018). Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps. Journal of Allergy and Clinical Immunology, 141(3), 927-937. https://doi.org/10.1016/j.jaci.2017.10.014

@article{9e1ae239780f4f99958380b197012415,

title = "Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps",

abstract = "Background: The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. Objective: We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP. Methods: We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cμ and Iε-Cγ circle transcripts was detected by using seminested PCR. Results: Increased formation of eLTs with germinal center–like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cμ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps. Conclusion: eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP.",

keywords = "Ectopic lymphoid tissue, immunoglobulin, lymphoid aggregate, lymphorganogenesis",

author = "Jia Song and Hai Wang and Zhang, {Ya Na} and Cao, {Ping Ping} and Bo Liao and Wang, {Zhe Zheng} and Shi, {Li Li} and Yin Yao and Zhai, {Guan Ting} and Wang, {Zhi Chao} and Liu, {Li Meng} and Ming Zeng and Xiang Lu and Heng Wang and Yang, {Xiang Ping} and Di Yu and Claus Bachert and Zheng Liu",

note = "Publisher Copyright: {\textcopyright} 2017 American Academy of Allergy, Asthma & Immunology",

year = "2018",

month = mar,

doi = "10.1016/j.jaci.2017.10.014",

language = "English",

volume = "141",

pages = "927--937",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

number = "3",

}

Song, J, Wang, H, Zhang, YN, Cao, PP, Liao, B, Wang, ZZ, Shi, LL, Yao, Y, Zhai, GT, Wang, ZC, Liu, LM, Zeng, M, Lu, X, Wang, H, Yang, XP, Yu, D, Bachert, C & Liu, Z 2018, 'Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps', Journal of Allergy and Clinical Immunology, vol. 141, no. 3, pp. 927-937. https://doi.org/10.1016/j.jaci.2017.10.014

TY - JOUR

T1 - Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps

AU - Song, Jia

AU - Wang, Hai

AU - Zhang, Ya Na

AU - Cao, Ping Ping

AU - Liao, Bo

AU - Wang, Zhe Zheng

AU - Shi, Li Li

AU - Yao, Yin

AU - Zhai, Guan Ting

AU - Wang, Zhi Chao

AU - Liu, Li Meng

AU - Zeng, Ming

AU - Lu, Xiang

AU - Wang, Heng

AU - Yang, Xiang Ping

AU - Yu, Di

AU - Bachert, Claus

AU - Liu, Zheng

PY - 2018/3

Y1 - 2018/3

N2 - Background: The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. Objective: We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP. Methods: We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cμ and Iε-Cγ circle transcripts was detected by using seminested PCR. Results: Increased formation of eLTs with germinal center–like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cμ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps. Conclusion: eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP.

AB - Background: The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. Objective: We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP. Methods: We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cμ and Iε-Cγ circle transcripts was detected by using seminested PCR. Results: Increased formation of eLTs with germinal center–like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cμ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps. Conclusion: eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP.

KW - Ectopic lymphoid tissue

KW - immunoglobulin

KW - lymphoid aggregate

KW - lymphorganogenesis

UR - http://www.scopus.com/inward/record.url?scp=85036645485&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2017.10.014

DO - 10.1016/j.jaci.2017.10.014

M3 - Article

SN - 0091-6749

VL - 141

SP - 927

EP - 937

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 3

ER -

Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps

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