title: BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis.
abstract: Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.
authors.affiliation: Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Mintao
authors.initials: M
authors.lastname: Hu
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Tingting
authors.initials: T
authors.lastname: Su
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000187:drug effects*; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism; D001629:Bezafibrate / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged
chemical_list: D053264:B-Cell Activating Factor; D016207:Cytokines; D001629:Bezafibrate