Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; School of Biomedical Engineering, Science, and Health Systems, Drexel University, PA, 19104, USA.
Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Cell Calcium. 2018 Sep;74:131-143. doi: 10.1016/j.ceca.2018.07.003. Epub 2018 Jul 10.
The central role of Ca signaling in the development of functional immunity and tolerance is well established. These signals are initiated by antigen binding to cognate receptors on lymphocytes that trigger store operated Ca entry (SOCE). The underlying mechanism of SOCE in lymphocytes involves TCR and BCR mediated activation of Stromal Interaction Molecule 1 and 2 (STIM1/2) molecules embedded in the ER membrane leading to their activation of Orai channels in the plasma membrane. STIM/Orai dependent Ca signals guide key antigen induced lymphocyte development and function principally through direct regulation of Ca dependent transcription factors. The role of Ca signaling in NFAT activation and signaling is well known and has been studied extensively, but a wide appreciation and mechanistic understanding of how Ca signals also shape the activation and specificity of NF-κB dependent gene expression has lagged. Here we discuss and interpret what is known about Ca dependent mechanisms of NF-kB activation, including what is known and the gaps in our understanding of how these signals control lymphocyte development and function.
Ca 信号在功能性免疫和耐受的发展中起着核心作用，这一点已得到充分证实。这些信号是由抗原与淋巴细胞上的同源受体结合引发的，从而触发储存操作的 Ca 内流 (SOCE)。淋巴细胞中 SOCE 的潜在机制涉及 TCR 和 BCR 介导的基质相互作用分子 1 和 2 (STIM1/2)分子在 ER 膜中的激活，导致它们在质膜中激活 Orai 通道。STIM/Orai 依赖性 Ca 信号指导关键的抗原诱导淋巴细胞发育和功能，主要是通过直接调节 Ca 依赖性转录因子。Ca 信号在 NFAT 激活和信号转导中的作用是众所周知的，并且已经进行了广泛的研究，但是对于 Ca 信号如何塑造 NF-κB 依赖性基因表达的激活和特异性的广泛认识和机制理解还存在滞后。在这里，我们讨论并解释了已知的 NF-kB 激活的 Ca 依赖性机制，包括已知的和我们对这些信号如何控制淋巴细胞发育和功能的理解中的空白。
