School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Front Immunol. 2022 Jun 29;13:886127. doi: 10.3389/fimmu.2022.886127. eCollection 2022.
The transcription factor family of nuclear factor kappa B (NF-κB) proteins is widely recognized as a key player in inflammation and the immune responses, where it plays a fundamental role in translating external inflammatory cues into precise transcriptional programs, including the timely expression of a wide variety of cytokines/chemokines. Live cell imaging in single cells showed approximately 15 years ago that the canonical activation of NF-κB upon stimulus is very dynamic, including oscillations of its nuclear localization with a period close to 1.5 hours. This observation has triggered a fruitful interdisciplinary research line that has provided novel insights on the NF-κB system: how its heterogeneous response differs between cell types but also within homogeneous populations; how NF-κB dynamics translate external cues into intracellular signals and how NF-κB dynamics affects gene expression. Here we review the main features of this live cell imaging approach to the study of NF-κB, highlighting the key findings, the existing gaps of knowledge and hinting towards some of the potential future steps of this thriving research field.
核因子 kappa B(NF-κB)蛋白转录因子家族被广泛认为是炎症和免疫反应的关键参与者,它在将外部炎症信号转化为精确的转录程序方面发挥着重要作用,包括及时表达各种细胞因子/趋化因子。大约 15 年前,在单细胞中的活细胞成像表明,刺激后 NF-κB 的经典激活非常动态,包括其核定位的振荡,其周期接近 1.5 小时。这一观察结果引发了一条富有成效的跨学科研究线,为 NF-κB 系统提供了新的见解:其异质反应如何在细胞类型之间以及在同质群体中有所不同;NF-κB 动力学如何将外部线索转化为细胞内信号,以及 NF-κB 动力学如何影响基因表达。在这里,我们回顾了这种用于研究 NF-κB 的活细胞成像方法的主要特点,强调了关键发现、现有知识空白,并暗示了这一蓬勃发展的研究领域的一些潜在未来步骤。