Triptolide Inhibits Tonsillar IgA Class Switching by Upregulating FDC-SP in IgA Nephropathy

IgA nephropathy (IgAN) is characterized by qualitative abnormality of IgA in affected tonsils, where present enhancement of IgA production by IgA class switching and immuno-activation. Follicular dendritic cell-secreted protein (FDC-SP) was found to be effective in tonsillar IgA production of IgAN. Triptolide, a core medicinal component of Tripterygium wilfordii, has been suggested to control IgA production by its' immunosuppression effect. Given this background, this study investigated the mechanisms underlying the role of Triptolide and FDC-SP in the generation of IgA and IgA class switching in tonsil of IgAN patients. Immunohistochemistry and reverse transcription-polymerase chain reaction revealed that the expression of FDC-SP were increased and was correlated negatively with decreased IgA inducing cytokines in the tonsils of IgAN patients with Triptolide treatment compared with those without treatment, followed by significantly decreased of IgA-bearing cells. The location of FDC-SP in tonsillar tissue was confirmed by double immunofluorescence. Importantly, Triptolide promoted FDC-SP secretion, and correlated negatively with decreased IgA production in isolated FDC-associated clusters. Our study demonstrated that Triptolide may be involved in IgA production in the tonsils of IgAN patients, inhibiting IgA class switching in IgAN patients through the cooperative roles of FDC-SP, highlighting a promising strategy for therapeutic intervention in IgAN.   Funding Statement: This work was supported by the National Nature Science Foundation of China (81600539), Natural Science Foundation of Heilongjiang Province of China (QC2012C041, LC2016038), Nn10 program of Harbin Medical University Cancer Hospital (Nn10 2017-03), Postdoctoral Science Start-up Foundation of Heilongjiang Province (Hongxue Meng), Harbin Special fund project for Science and technology innovation(2016RAQXJ203), Youth elite training Foundation of Harbin Medical University Cancer Hospital (JY2016-06) and Outstanding Youth Foundation of Harbin Medical University Cancer Hospital (JCQN-2018-05)，Clinical Scientific Research Foundation of China Medical and Health Development Foundation (Hongxue Meng), Harbin Medical University Postgraduate Research and Practice Innovation Project (Huining Li). Declaration of Interests: All authors have read the journal's policy on disclosure of potential conflicts of interest and have none to declare. Ethics Approval Statement: This research was carried out according to the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants in this study. Approval for this study was obtained from the Medical Ethics Committees of First Affiliated Hospital of Hei Longjiang University of Chinese Medicine (HZYLLBA201714).