Tripterygium Wilfordii inhibits tonsillar IgA production by downregulating IgA class switching in IgA nephropathy
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Huining Li1,2,3,*, Dan Kong4,*, Yangyang Xu5,*, Xiaomei Li2, Guodong Yao2, Kexin Chen2, Qi You6, Qingtao Shi2, Lei Zhang1, Xin Wang7, Dawei Yuan9, Shusheng Miao8, Jingshu Geng2, Xiaoming Jin1 and Hongxue Meng2
1Department of Pathology, Harbin Medical University, Harbin, China
2Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China
3Department of Pathology, The First Affiliated Hospital of Hei Longjiang University of Chinese Medicine, Harbin, China
4Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, China
5Department of Urinary Surgery, Harbin Medical University Cancer Hospital, Harbin, China
6Department of Gastroenterology, Harbin Medical University Cancer Hospital, Harbin, China
7Department of Otolaryngology, Head and Neck Surgery, Second Hospital Affiliated to Harbin Medical University, Harbin, China
8Department of Otolaryngology, Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, China
9Geneis (Beijing) Co.Ltd, Beijing, China
*Huining Li, Dan Kong and Yangyang Xu contributed equally to this study
Xiaoming Jin, email: [email protected]
Hongxue Meng, email: [email protected]
Keywords: Tripterygium Wilfordii; IgA nephropathy; tonsil; thymic stromal lymphopoietin; IgA class switching
Received: May 30, 2017 Accepted: October 04, 2017 Published: November 20, 2017
IgA nephropathy (IgAN) is characterized by high serum IgA levels and IgA deposition in the renal mesangium. Recent research has indicated that pathogenic IgA may originate from affected tonsils, where present enhancement of IgA production by IgA class switching and immuno-activation. Tripterygium Wilfordii (TW) was found to be especially effective in IgAN by its’ immunosuppression effect. Given this background, we investigated the mechanisms underlying the role of TW in the generation of IgA and IgA class switching in tonsillar GCs of IgAN patients. Immunohistochemistry and RT-PCR revealed that the expression of thymic stromal lymphopoietin (TSLP) and IgA inducing cytokines were decreased in the tonsils of IgAN patients with TW treatment compared with those without treatment, followed by significantly decreased of IgA-bearing cells. The location of TSLP and IgA inducing cytokines in tonsillar tissue was confirmed by double immunofluorescence. Importantly, TW inhibit TSLP and IgA production in isolated FDC-associated clusters. Serum TSLP levels were decreased and correlated with IgA downregulation in the tonsils and serum of IgAN patients. These data indicated that TW may be involved in IgA production in the tonsils of IgAN patients, inhibiting IgA class switching in IgAN patients through the cooperative roles of AID, TGF-β1, BAFF, and APRIL, highlighting a promising strategy for therapeutic intervention in IgAN.
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