Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Department of Immunology, Institute of Immunity and Transplantation, Royal Free Hospital, London, UK.
Adv Exp Med Biol. 2020;1227:145-164. doi: 10.1007/978-3-030-36422-9_10.
Notch is a ligand-receptor interaction-triggered signaling cascade highly conserved, that influences multiple lineage decisions within the hematopoietic and the immune system. It is a recognized model of intercellular communication that plays an essential role in embryonic as well as in adult immune cell development and homeostasis. Four members belong to the family of Notch receptors (Notch1-4), and each of them plays nonredundant functions at several developmental stages. Canonical and noncanonical pathways of Notch signaling are multifaceted drivers of immune cells biology. In fact, increasing evidence highlighted Notch as an important modulator of immune responses, also in cancer microenvironment. In these contexts, multiple transduction signals, including canonical and alternative NF-κB pathways, play a relevant role. In this chapter, we will first describe the critical role of Notch and NF-κB signals in lymphoid lineages developing in thymus: natural killer T cells, thymocytes, and thymic T regulatory cells. We will address also the role played by ligand expressing cells. Given the importance of Notch/NF-κB cross talk, its role in T-cell leukemia development and progression will be discussed.
Notch 是一个配体-受体相互作用触发的信号级联反应，高度保守，影响造血系统和免疫系统中的多个谱系决定。它是细胞间通讯的公认模型，在胚胎和成人免疫细胞发育和稳态中发挥着重要作用。Notch 受体家族有四个成员（Notch1-4），它们在几个发育阶段发挥着非冗余的作用。Notch 信号的经典和非经典途径是免疫细胞生物学的多方面驱动因素。事实上，越来越多的证据表明 Notch 是免疫反应的重要调节剂，在肿瘤微环境中也是如此。在这些情况下，包括经典和替代 NF-κB 途径在内的多种转导信号发挥着重要作用。在本章中，我们将首先描述 Notch 和 NF-κB 信号在胸腺中淋巴细胞谱系发育中的关键作用：自然杀伤 T 细胞、胸腺细胞和胸腺 T 调节细胞。我们还将讨论配体表达细胞所起的作用。鉴于 Notch/NF-κB 串扰的重要性，将讨论其在 T 细胞白血病发生和进展中的作用。
