Department of Internal Medicine, Spital Limmattal, Schlieren, Switzerland.
Department of Internal Medicine, University of Zurich and University Hospital of Zurich, Zurich, Switzerland.
Adv Exp Med Biol. 2024;1459:159-195. doi: 10.1007/978-3-031-62731-6_8.
NFE2-related factor 2 (NRF2) is a master transcription factor (TF) that coordinates key cellular homeostatic processes including antioxidative responses, autophagy, proteostasis, and metabolism. The emerging evidence underscores its significant role in modulating inflammatory and immune processes. This chapter delves into the role of NRF2 in myeloid cell differentiation and function and its implication in myeloid cell-driven diseases. In macrophages, NRF2 modulates cytokine production, phagocytosis, pathogen clearance, and metabolic adaptations. In dendritic cells (DCs), it affects maturation, cytokine production, and antigen presentation capabilities, while in neutrophils, NRF2 is involved in activation, migration, cytokine production, and NETosis. The discussion extends to how NRF2's regulatory actions pertain to a wide array of diseases, such as sepsis, various infectious diseases, cancer, wound healing, atherosclerosis, hemolytic conditions, pulmonary disorders, hemorrhagic events, and autoimmune diseases. The activation of NRF2 typically reduces inflammation, thereby modifying disease outcomes. This highlights the therapeutic potential of NRF2 modulation in treating myeloid cell-driven pathologies.
NFE2 相关因子 2（NRF2）是一种主要的转录因子（TF），它协调包括抗氧化反应、自噬、蛋白稳态和代谢在内的关键细胞内稳态过程。新出现的证据强调了它在调节炎症和免疫过程中的重要作用。本章探讨了 NRF2 在髓样细胞分化和功能中的作用及其在髓样细胞驱动的疾病中的意义。在巨噬细胞中，NRF2 调节细胞因子产生、吞噬作用、病原体清除和代谢适应。在树突状细胞（DC）中，它影响成熟、细胞因子产生和抗原呈递能力，而在中性粒细胞中，NRF2 参与激活、迁移、细胞因子产生和 NETosis。讨论还扩展到了 NRF2 的调节作用如何涉及到广泛的疾病，如败血症、各种传染病、癌症、伤口愈合、动脉粥样硬化、溶血性疾病、肺部疾病、出血事件和自身免疫性疾病。NRF2 的激活通常会减轻炎症，从而改变疾病的结局。这突出了 NRF2 调节在治疗髓样细胞驱动的病理中的治疗潜力。
