Leiba Jade, Özbilgiç Resul, Hernández Liz, Demou Maria, Lutfalla Georges, Yatime Laure, Nguyen-Chi Mai
Laboratory of Pathogens and Host Immunity (LPHI) UMR5294, University of Montpellier, CNRS, INSERM, 34095 Montpellier, France.
Biology (Basel). 2023 Jan 19;12(2):153. doi: 10.3390/biology12020153.
Inflammation is a hallmark of the physiological response to aggressions. It is orchestrated by a plethora of molecules that detect the danger, signal intracellularly, and activate immune mechanisms to fight the threat. Understanding these processes at a level that allows to modulate their fate in a pathological context strongly relies on in vivo studies, as these can capture the complexity of the whole process and integrate the intricate interplay between the cellular and molecular actors of inflammation. Over the years, zebrafish has proven to be a well-recognized model to study immune responses linked to human physiopathology. We here provide a systematic review of the molecular effectors of inflammation known in this vertebrate and recapitulate their modes of action, as inferred from sterile or infection-based inflammatory models. We present a comprehensive analysis of their sequence, expression, and tissue distribution and summarize the tools that have been developed to study their function. We further highlight how these tools helped gain insights into the mechanisms of immune cell activation, induction, or resolution of inflammation, by uncovering downstream receptors and signaling pathways. These progresses pave the way for more refined models of inflammation, mimicking human diseases and enabling drug development using zebrafish models.
炎症是机体对侵袭产生生理反应的一个标志。它由大量检测危险、在细胞内发出信号并激活免疫机制以对抗威胁的分子精心调控。要在能够调节其在病理情况下转归的层面理解这些过程，很大程度上依赖于体内研究，因为体内研究能够捕捉整个过程的复杂性，并整合炎症的细胞和分子参与者之间错综复杂的相互作用。多年来，斑马鱼已被证明是研究与人类生理病理学相关免疫反应的一个广为人知的模型。我们在此对这种脊椎动物中已知的炎症分子效应器进行系统综述，并概括它们的作用模式，这些作用模式是从无菌或基于感染的炎症模型中推断出来的。我们对它们的序列、表达和组织分布进行全面分析，并总结已开发出的用于研究其功能的工具。我们还进一步强调这些工具如何通过揭示下游受体和信号通路，帮助深入了解免疫细胞激活、炎症诱导或消退的机制。这些进展为更精确的炎症模型铺平了道路，这些模型可模拟人类疾病并利用斑马鱼模型进行药物研发。
