Abstract
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.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Cited by
6 articles.
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