Müller Ludmila, Di Benedetto Svetlana, Müller Viktor
Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany.
Cells. 2025 Jan 5;14(1):54. doi: 10.3390/cells14010054.
Neuroinflammation is a complex and multifaceted process that involves dynamic interactions among various cellular and molecular components. This sophisticated interplay supports both environmental adaptability and system resilience in the central nervous system (CNS) but may be disrupted during neuroinflammation. In this article, we first characterize the key players in neuroimmune interactions, including microglia, astrocytes, neurons, immune cells, and essential signaling molecules such as cytokines, neurotransmitters, extracellular matrix (ECM) components, and neurotrophic factors. Under homeostatic conditions, these elements promote cellular cooperation and stability, whereas in neuroinflammatory states, they drive adaptive responses that may become pathological if dysregulated. We examine how neuroimmune interactions, mediated through these cellular actors and signaling pathways, create complex networks that regulate CNS functionality and respond to injury or inflammation. To further elucidate these dynamics, we provide insights using a multilayer network (MLN) approach, highlighting the interconnected nature of neuroimmune interactions under both inflammatory and homeostatic conditions. This perspective aims to enhance our understanding of neuroimmune communication and the mechanisms underlying shifts from homeostasis to neuroinflammation. Applying an MLN approach offers a more integrative view of CNS resilience and adaptability, helping to clarify inflammatory processes and identify novel intervention points within the layered landscape of neuroinflammatory responses.
神经炎症是一个复杂且多层面的过程，涉及各种细胞和分子成分之间的动态相互作用。这种复杂的相互作用既支持中枢神经系统（CNS）的环境适应性和系统弹性，也可能在神经炎症期间被破坏。在本文中，我们首先描述神经免疫相互作用中的关键参与者，包括小胶质细胞、星形胶质细胞、神经元、免疫细胞以及细胞因子、神经递质、细胞外基质（ECM）成分和神经营养因子等重要信号分子。在稳态条件下，这些成分促进细胞合作与稳定性，而在神经炎症状态下，它们驱动适应性反应，如果调节失调，这些反应可能会变得病理性。我们研究通过这些细胞参与者和信号通路介导的神经免疫相互作用如何创建调节中枢神经系统功能并对损伤或炎症作出反应的复杂网络。为了进一步阐明这些动态变化，我们使用多层网络（MLN）方法提供见解，强调炎症和稳态条件下神经免疫相互作用的相互连接性质。这一观点旨在增进我们对神经免疫通信以及从稳态转变为神经炎症的潜在机制的理解。应用MLN方法可提供对中枢神经系统弹性和适应性的更综合观点，有助于阐明炎症过程并在神经炎症反应的分层景观中确定新的干预点。
