Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110169, China.
Sci Rep. 2017 Mar 23;7:44809. doi: 10.1038/srep44809.
BAP31 is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein. The functions of BAP31 in the immune system have not been investigated due to the lack of animal models. Therefore we created a BAP31 conditional knockdown mouse by performing a knockdown of BAP31 in the thymus. In doing so, we demonstrate that the maturation of T cells is normal but the number of T cells is less in the thymus of the knockout mouse. In addition, the spleen and lymph nodes of peripheral immune organs contained a lesser proportion of the mature T cells in the thymus specific BAP31 knockout mice. The BAP31 knockout T cells decreased the proliferation activated by TCR signal pathways. Further studies clarified that BAP31 affects the phosphorylation levels of both Zap70/Lck/Lat of the upstream members and Akt/GSK/Jnk/Erk of the downstream members of TCR signal pathways. Furthermore, BAP31 can regulate the expression of some markers such as CD3/TCRα/TCRβ and some cytokines like IL-2/IFN-γ/IL-6/TNF-α which are important for T cell activation. Taken together, these results demonstrate that BAP31 may play an important role in T cell activation by regulating TCR signaling.
BAP31 是一种普遍表达的内质网（ER）膜蛋白。由于缺乏动物模型，BAP31 在免疫系统中的功能尚未得到研究。因此，我们通过在胸腺中敲低 BAP31 来创建 BAP31 条件性敲低小鼠。通过这样做，我们证明 T 细胞的成熟是正常的，但敲除小鼠的胸腺中 T 细胞的数量较少。此外，在胸腺特异性 BAP31 敲除小鼠的外周免疫器官脾和淋巴结中，成熟 T 细胞的比例较低。BAP31 敲除 T 细胞减少了 TCR 信号通路激活的增殖。进一步的研究表明，BAP31 影响 TCR 信号通路上游成员的 Zap70/Lck/Lat 和下游成员的 Akt/GSK/Jnk/Erk 的磷酸化水平。此外，BAP31 可以调节一些标记物的表达，如 CD3/TCRα/TCRβ 和一些细胞因子，如 IL-2/IFN-γ/IL-6/TNF-α，这些对于 T 细胞激活很重要。总之，这些结果表明 BAP31 可能通过调节 TCR 信号在 T 细胞激活中发挥重要作用。
