Gallenstein Nadia, Tichy Lucas, Weigand Markus Alexander, Schenz Judith
Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Int J Mol Sci. 2023 Feb 9;24(4):3458. doi: 10.3390/ijms24043458.
Notch signaling, a highly conserved pathway in mammals, is crucial for differentiation and homeostasis of immune cells. Besides, this pathway is also directly involved in the transmission of immune signals. Notch signaling per se does not have a clear pro- or anti-inflammatory effect, but rather its impact is highly dependent on the immune cell type and the cellular environment, modulating several inflammatory conditions including sepsis, and therefore significantly impacts the course of disease. In this review, we will discuss the contribution of Notch signaling on the clinical picture of systemic inflammatory diseases, especially sepsis. Specifically, we will review its role during immune cell development and its contribution to the modulation of organ-specific immune responses. Finally, we will evaluate to what extent manipulation of the Notch signaling pathway could be a future therapeutic strategy.
Notch信号通路在哺乳动物中是一条高度保守的信号通路,对免疫细胞的分化和内环境稳定至关重要。此外,该信号通路还直接参与免疫信号的传递。Notch信号通路本身并没有明确的促炎或抗炎作用,其影响高度依赖于免疫细胞类型和细胞环境,可调节包括脓毒症在内的多种炎症状态,因此对疾病进程有显著影响。在本综述中,我们将讨论Notch信号通路对全身性炎症疾病,尤其是脓毒症临床表现的作用。具体而言,我们将综述其在免疫细胞发育过程中的作用及其对器官特异性免疫反应调节的贡献。最后,我们将评估Notch信号通路的调控在多大程度上可能成为未来的治疗策略。