From Homeostasis to Neuroinflammation: Insights into Cellular and Molecular Interactions and Network Dynamics.

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.