Metwally Hozaifa
Laboratory of Immune Regulation, The World Premier International Research Center Initiative (WPI) Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
Biomolecules. 2025 Mar 26;15(4):487. doi: 10.3390/biom15040487.
Immunity is a fundamental aspect of animal biology, defined as the host's ability to detect and defend against harmful pathogens and toxic substances to preserve homeostasis. However, immune defenses are metabolically demanding, requiring the efficient allocation of limited resources to balance immune function with other physiological and developmental needs. To achieve this balance, organisms have evolved sophisticated signaling networks that enable precise, context-specific responses to internal and external cues. These networks are essential for survival and adaptation in multicellular systems. Central to this regulatory architecture is the STAT (signal transducer and activator of Transcription) family, a group of versatile signaling molecules that govern a wide array of biological processes across eukaryotes. STAT signaling demonstrates remarkable plasticity, from orchestrating host defense mechanisms to regulating dietary metabolism. Despite its critical role, the cell-specific and context-dependent nuances of STAT signaling remain incompletely understood, highlighting a significant gap in our understanding. This review delves into emerging perspectives on immunity, presenting dynamic frameworks to explore the complexity and adaptability of STAT signaling and the underlying logic driving cellular decision-making. It emphasizes how STAT pathways integrate diverse physiological processes, from immune responses to dietary regulation, ultimately supporting organismal balance and homeostasis.
免疫是动物生物学的一个基本方面，定义为宿主检测和抵御有害病原体及有毒物质以维持体内平衡的能力。然而，免疫防御对代谢要求很高，需要有效分配有限资源，以平衡免疫功能与其他生理和发育需求。为实现这种平衡，生物体进化出了复杂的信号网络，能够对内部和外部线索做出精确的、针对具体情况的反应。这些网络对于多细胞系统中的生存和适应至关重要。这种调节结构的核心是STAT（信号转导和转录激活因子）家族，这是一组多功能信号分子，在整个真核生物中控制着广泛的生物过程。STAT信号表现出显著的可塑性，从协调宿主防御机制到调节饮食代谢。尽管其作用至关重要，但STAT信号在细胞特异性和依赖于具体情况的细微差别仍未完全被理解，这凸显了我们理解上的重大差距。本综述深入探讨了免疫方面的新观点，提出了动态框架，以探索STAT信号的复杂性和适应性以及驱动细胞决策的潜在逻辑。它强调了STAT通路如何整合从免疫反应到饮食调节等多种生理过程，最终支持机体平衡和体内平衡。
