Institute of Biology Leiden, Leiden University, The Netherlands.
Institute of Biology Leiden, Leiden University, The Netherlands.
Gen Comp Endocrinol. 2024 Jan 1;345:114387. doi: 10.1016/j.ygcen.2023.114387. Epub 2023 Oct 1.
Stressors in the environment of aquatic organisms can profoundly affect their immune system. The stress response in fish involves the activation of the hypothalamus-pituitary-interrenal (HPI) axis, leading to the release of several stress hormones, among them glucocorticoids, such as cortisol, which bind and activate corticosteroid receptors, namely the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). These receptors are highly expressed on immune cells, thereby allowing stress to have a potent effect that is classically considered to suppress immune function. In this review, we highlight the conserved structure and function of GR and MR among vertebrates and describe their role in modulating inflammation by regulating the expression of pro-inflammatory and anti-inflammatory genes. In particular, the involvement of MR during inflammation is reviewed, which in many studies has been shown to be immune-enhancing. In recent years, the use of zebrafish as a model organism has opened up new possibilities to study the effects of stress on inflammation, making it possible to investigate knockout lines for MR and/or GR, in combination with transgenic models with fluorescently labeled leukocyte subpopulations that enable the visualization and manipulation of these immune cells. The potential roles of other hormones of the HPI axis, such as corticotrophin-releasing hormone (Crh) and adrenocorticotropic hormone (Acth), in immune modulation are also discussed. Overall, this review highlights the need for further research to elucidate the specific roles of GR, MR and other stress hormones in regulating immune function in fish. Understanding these mechanisms will contribute to improving fish health and advancing our knowledge of stress signalling.
环境中的应激原会对水生生物的免疫系统产生深远影响。鱼类的应激反应涉及下丘脑-垂体-肾上腺（HPI）轴的激活，导致多种应激激素的释放，其中包括皮质醇等糖皮质激素，它们与糖皮质激素受体（GR）和盐皮质激素受体（MR）结合并激活这些受体。这些受体在免疫细胞上高度表达，从而使应激能够产生强大的作用，这种作用通常被认为是抑制免疫功能。在这篇综述中，我们强调了 GR 和 MR 在脊椎动物中的保守结构和功能，并描述了它们通过调节促炎和抗炎基因的表达来调节炎症的作用。特别是，我们回顾了 MR 在炎症中的作用，许多研究表明，MR 具有增强免疫的作用。近年来，斑马鱼作为一种模式生物的使用为研究应激对炎症的影响开辟了新的可能性，使我们能够研究 MR 和/或 GR 的敲除系，并结合荧光标记白细胞亚群的转基因模型，从而能够可视化和操纵这些免疫细胞。我们还讨论了 HPI 轴的其他激素，如促肾上腺皮质激素释放激素（CRH）和促肾上腺皮质激素（ACTH）在免疫调节中的潜在作用。总的来说，这篇综述强调了需要进一步研究以阐明 GR、MR 和其他应激激素在调节鱼类免疫功能中的具体作用。了解这些机制将有助于改善鱼类健康并推进我们对应激信号的认识。
