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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Research

TSLP promoting B cell proliferation and polarizing follicular helper T cell as a therapeutic target in IgG4-related disease

Authors: Hui Lu, Xunyao Wu, Yu Peng, Ruijie Sun, Yuxue Nie, Jingna Li, Mu Wang, Yaping Luo, Linyi Peng, Yunyun Fei, Jiaxin Zhou, Wen Zhang, Xiaofeng Zeng

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Objective

To figure out the functions of thymic stromal lymphopoietin (TSLP) in IgG4-related disease (IgG4-RD).

Methods

Plasma TSLP levels were tested by Elisa, and its receptors were detected by flow cytometry. Expressions of TSLP and TSLPR in involved tissues were stained by immunohistochemistry and immunofluorescence. Proliferation, apoptosis, and B subsets of TSLP stimulated-B cells were analyzed by flow cytometry. TSLP-stimulated B cells were co-cultured with CD4+ Naïve T cells. Signaling pathway was identified by RNA-sequencing and western blot. Anti-TSLP therapy was adapted in LatY136F knock-in mice (Lat, IgG4-RD mouse model).

Results

Plasma TSLP level was increased in IgG4-RD patients and was positively correlated with serum IgG4 level and responder index (RI). TSLPR was co-localized with CD19+ B cells in the submandibular glands (SMGs) of IgG4-RD. TSLP promoted B cell proliferation, and TSLP-activated B cells polarized CD4+ naive T cells into follicular helper T (Tfh) cells through OX40L. RNA-sequencing identified JAK-STAT signaling pathway in TSLP-activated B cells and it was verified by western blot. Anti-TSLP therapy alleviated the inflammation of lung in Lat mice.

Conclusion

Elevated TSLP in IgG4-RD promoted B cells proliferation and polarized Tfh cells and might be served as a potential therapeutic target.
Appendix
Available only for authorised users
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Metadata
Title
TSLP promoting B cell proliferation and polarizing follicular helper T cell as a therapeutic target in IgG4-related disease
Authors
Hui Lu
Xunyao Wu
Yu Peng
Ruijie Sun
Yuxue Nie
Jingna Li
Mu Wang
Yaping Luo
Linyi Peng
Yunyun Fei
Jiaxin Zhou
Wen Zhang
Xiaofeng Zeng
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03606-1

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