Cellular state transitions in neuroimmune disorders
TL;DR
This perspective provides a unifying conceptual framework for understanding neuroimmune pathology in disorders such as Alzheimer’s disease, multiple sclerosis, stroke, and traumatic brain injury, while also pointing toward next-generation strategies that selectively modulate maladaptive cellular programs and promote regenerative neuroimmune states.
Abstract
Neuroimmune disorders are increasingly understood not as the consequence of dysfunction in isolated cell types, but as dynamic diseases shaped by coordinated transitions across interacting neural and immune cell states. This narrative review synthesizes current evidence showing how microglia, astrocytes, neural stem cells, vascular elements, and infiltrating peripheral immune cells shift between homeostatic, inflammatory, reparative, and disease-associated states in response to injury, infection, degeneration, and metabolic stress. We highlight how cytokine signaling, damage-associated molecular patterns, oxidative and metabolic stress, and transcriptional and epigenetic reprogramming reshape neuroimmune behavior across these cellular populations, thereby influencing inflammation, synaptic remodeling, tissue repair, and disease progression. By framing neurological disorders as state transition networks rather than static cellular abnormalities, this review integrates emerging insights from single-cell and spatial profiling with systems-level neuroimmunology and identifies cellular plasticity as both a mechanistic principle and a therapeutic opportunity. This perspective provides a unifying conceptual framework for understanding neuroimmune pathology in disorders such as Alzheimer’s disease, multiple sclerosis, stroke, and traumatic brain injury, while also pointing toward next-generation strategies that selectively modulate maladaptive cellular programs and promote regenerative neuroimmune states.