Myeloid Cell Dynamics in Central Nervous System Function and Disease

Myeloid cells in the central nervous system (CNS) encompass resident microglia and diverse populations of border‐associated macrophages that constantly survey, sculpt and defend neural tissue. During development, these cells regulate neuronal proliferation, synaptic pruning and myelin formation, while in adulthood they maintain homeostasis through debris clearance and trophic support. In response to injury or pathology, myeloid cells adopt distinct activation profiles—ranging from pro‐inflammatory to reparative—that influence disease progression in conditions such as multiple sclerosis, Alzheimer’s disease and brain tumours. Recent advances reveal that transitions between functional states are governed by tightly controlled transcriptional programmes, epigenetic landscapes and intercellular crosstalk. A comprehensive understanding of these dynamic processes offers routes to modulate immune responses for therapeutic gain, underscoring the global significance of myeloid cell biology in CNS health and disease.

Research from Nature Portfolio

Integrated multiomic analysis of human CNS borders has mapped resident and engrafted myeloid populations at unprecedented resolution, revealing compartment-specific engraftment rates and distinct hypoxia-driven myeloid distributions within glioblastoma. In Alzheimer’s models, perivascular macrophage–derived osteopontin was shown to induce microglial phagocytic states and synaptic engulfment, demonstrating a critical ligand-receptor axis that drives synapse loss. Mechanistic studies of microglial identity uncovered a microglia-specific super-enhancer at the Sall1 locus, where SALL1 and SMAD4 cooperate to enforce TGFβ signalling programmes and restrict off-target enhancer activation, thereby stabilising core homeostatic functions.

Myeloid Cell Dynamics in Central Nervous System Function and Disease publication trend

The graph below shows the total number of articles in myeloid cell dynamics in central nervous system function and disease across all publications each year (not limited to Nature Index journals).

Technical terms

Microglia: Resident macrophages of the CNS that monitor and maintain neural tissue integrity.

CNS-associated macrophages (CAMs): Myeloid cells located at CNS interfaces (perivascular, meningeal and choroid plexus) that complement microglial functions.

Single-cell RNA sequencing: High-throughput method for profiling gene expression in individual cells to reveal cellular diversity and state transitions.

Super-enhancer: Cluster of regulatory DNA elements that drives high-level, cell type–specific gene expression.

Osteopontin (SPP1): Secreted phosphoprotein that mediates signalling between perivascular macrophages and microglia to regulate phagocytic activation.

References

1. Multiomic spatial landscape of innate immune cells at human central nervous system borders. Nature Medicine (2023).
2. Type-I-interferon-responsive microglia shape cortical development and behavior. Cell (2024).
3. Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer’s disease. Nature Neuroscience (2023).
4. SALL1 enforces microglia-specific DNA binding and function of SMADs to establish microglia identity. Nature Immunology (2023).
5. Microglia states and nomenclature: A field at its crossroads. Neuron (2022).
6. Microglia Heterogeneity in the Single-Cell Era. Cell Reports (2020).