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Provedor de dados: |
56
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País: |
Brazil
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Título: |
BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis
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Autores: |
Zhang,Bo
Hu,Mintao
Zhang,Peng
Cao,Hong
Wang,Yongzhen
Wang,Zheng
Su,Tingting
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Data: |
2013-05-01
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Ano: |
2013
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Palavras-chave: |
Primary biliary cirrhosis
Regulatory T cells
BAFF
B cells
Bezafibrate
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Resumo: |
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.
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Tipo: |
Info:eu-repo/semantics/article
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Idioma: |
Inglês
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Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013000500433
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Editor: |
Associação Brasileira de Divulgação Científica
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Relação: |
10.1590/1414-431X20132665
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Formato: |
text/html
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Fonte: |
Brazilian Journal of Medical and Biological Research v.46 n.5 2013
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Direitos: |
info:eu-repo/semantics/openAccess
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