Zhang Lei, Dang Rui-Jie, Yang Yan-Mei, Cui Dian-Chao, Li Ping, Ni Yan-Li, Hao Tong, Wang Changyong, Jiang Xiao-Xia, Fang Nan-Zhu
Laboratory of Animal Genetic Breeding and Reproduction, Yanbian University, Yanji, Jilin 133002, China ; Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China ; Department of Biology and Chemical Engineering, Tongren University, Tongren, Guizhou 554300, China.
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
Stem Cells Int. 2016;2016:1628352. doi: 10.1155/2016/1628352. Epub 2015 Nov 16.
As stromal cells and recently confirmed mesenchymal stem cells, OP9 cells support hematopoiesis stem cell (HSC) differentiation into the B lymphocyte lineage, yet Delta-like-1 (DL1) overexpressing OP9 (OP9DL1) cells promote the development of early T lymphocytes from HSC. However, the immunomodulatory capacity of OP9 or OP9DL1 on mature B and T cell proliferation has not been elucidated. Here, we show that OP9 and OP9DL1 have similar proliferation capacities and immunophenotypes except DL1 expression. Compared with OP9, OP9DL1 displayed more osteogenesis and less adipogenesis when cultured in the respective induction media. Both OP9 and OP9DL1 inhibited mature B and T cell proliferation. Furthermore, OP9 showed stronger inhibition on B cell proliferation and OP9DL1 exhibited stronger inhibition on T cell proliferation. With stimulation, both OP9 and OP9DL1 showed increased nitrate oxide (NO) production. The NO levels of OP9 were higher than that of OP9DL1 when stimulated with TNFα/IFNγ or LPS/IL4. Taken together, our study reveals a previously unrecognized role of OP9 and OP9DL1 in mature B and T cell proliferation. DL1 overexpression alone changed the properties of OP9 cells in addition to their role in early B cell development.
作为基质细胞以及最近被证实的间充质干细胞,OP9细胞支持造血干细胞(HSC)分化为B淋巴细胞谱系,而过量表达Delta样-1(DL1)的OP9(OP9DL1)细胞则促进HSC发育为早期T淋巴细胞。然而,OP9或OP9DL1对成熟B细胞和T细胞增殖的免疫调节能力尚未阐明。在此,我们表明,除了DL1表达外,OP9和OP9DL1具有相似的增殖能力和免疫表型。与OP9相比,OP9DL1在各自的诱导培养基中培养时表现出更多的成骨作用和更少的脂肪生成。OP9和OP9DL1均抑制成熟B细胞和T细胞的增殖。此外,OP9对B细胞增殖的抑制作用更强,而OP9DL1对T细胞增殖的抑制作用更强。在受到刺激时,OP9和OP9DL1均显示出一氧化氮(NO)生成增加。在用TNFα/IFNγ或LPS/IL4刺激时,OP9的NO水平高于OP9DL1。综上所述,我们的研究揭示了OP9和OP9DL1在成熟B细胞和T细胞增殖中以前未被认识到的作用。单独的DL1过表达除了在早期B细胞发育中的作用外,还改变了OP9细胞的特性。