Signaling Systems Section, Laboratory of Immune System Biology, NIAID, DIR, NIH, Bethesda, MD, United States.
Front Immunol. 2019 Apr 9;10:705. doi: 10.3389/fimmu.2019.00705. eCollection 2019.
The nuclear factor-κB (NF-κB) signaling pathway is one of the best understood immune-related pathways thanks to almost four decades of intense research. NF-κB signaling is activated by numerous discrete stimuli and is a master regulator of the inflammatory response to pathogens and cancerous cells, as well as a key regulator of autoimmune diseases. In this regard, the role of NF-κB signaling in immunity is not unlike that of the macrophage. The dynamics by which NF-κB proteins shuttle between the cytoplasm and the nucleus to initiate transcription have been studied rigorously in fibroblasts and other non-hematopoietic cells, but many questions remain as to how current models of NF-κB signaling and dynamics can be translated to innate immune cells such as macrophages. In this review, we will present recent research on the dynamics of NF-κB signaling and focus especially on how these dynamics vary in different cell types, while discussing why these characteristics may be important. We will end by looking ahead to how new techniques and technologies should allow us to analyze these signaling processes with greater clarity, bringing us closer to a more complete understanding of inflammatory transcription factor dynamics and how different cellular contexts might allow for appropriate control of innate immune responses.
核因子-κB（NF-κB）信号通路是研究最为深入的免疫相关通路之一，这要归功于近四十年的深入研究。NF-κB 信号通路可被多种不同的刺激激活，是病原体和癌细胞炎症反应的主要调节因子，也是自身免疫性疾病的关键调节因子。在这方面，NF-κB 信号通路在免疫中的作用与巨噬细胞的作用类似。NF-κB 蛋白在细胞质和细胞核之间穿梭以启动转录的动力学已在成纤维细胞和其他非造血细胞中进行了严格研究，但对于如何将 NF-κB 信号转导和动力学的现有模型转化为先天免疫细胞（如巨噬细胞），仍存在许多问题。在这篇综述中，我们将介绍 NF-κB 信号转导动力学的最新研究进展，并特别关注这些动力学在不同细胞类型中的变化，同时讨论为什么这些特征可能很重要。最后，我们将展望新技术和技术如何使我们能够更清晰地分析这些信号转导过程，使我们更接近对炎症转录因子动力学的更全面理解，以及不同的细胞环境如何允许对先天免疫反应进行适当控制。
