期刊
JOURNAL OF IMMUNOLOGY
卷 199, 期 9, 页码 3063-3073出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1700138
关键词
-
类别
资金
- National Science Foundation China [81730043, 81422020, 81621002, 81671604]
- Ministry of Science and Technology of China [2014CB542500-03]
Unlike conventional B cells, regulatory B cells exhibit immunosuppressive functions to downregulate inflammation via IL-10 production. However, the molecular mechanism regulating the production of IL-10 is not fully understood. In this study, we report the finding that activation-induced cytidine deaminase (AID) is highly upregulated in the IL-10-competent B cell (B10) cell from Innp5d(fl/fl) Aicda(Cre/+) mice, whereas the 5 ' inositol phosphatase SHIP-1 is downregulated. Notably, SHIP-1 deficiency in AID(+) B cells leads to a reduction in cell count and impaired IL-10 production by B10 cells. Furthermore, the Innp5d(fl/fl) Aicda(Cre/+) mouse model shows B cell-dependent autoimmune lupus-like phenotypes, such as elevated IgG serum Abs, formation of spontaneous germinal centers, production of anti-dsDNA and anti-nuclear Abs, and the obvious deposition of IgG immune complexes in the kidney with age. We observe that these lupus-like phenotypes can be reversed by the adoptive transfer of B10 cells from control Innp5d(fl/fl) mice, but not from the Innp5d(fl/fl) Aicda(Cre/+) mice. This finding highlights the importance of defective B10 cells in Innp5d(fl/fl) Aicda(Cre/+) mice. Whereas p-Akt is significantly upregulated, MAPK and AP-1 activation is impaired in B10 cells from Innp5d(fl/fl) Aicda(Cre/+) mice, resulting in the reduced production of IL-10. These results show that SHIP-1 is required for the maintenance of B10 cells and production of IL-10, and collectively suggests that SHIP-1 could be a new potential therapeutic target for the treatment of autoimmune diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据