Immunological Mechanisms in Central Nervous System Disorders

The central nervous system (CNS) has long been regarded as an immune-privileged site, yet growing evidence highlights a dynamic interplay between resident glial cells and peripheral immune populations in health and disease. Microglia and astrocytes act as first responders to pathogens and injury, releasing cytokines and chemokines that influence blood–brain barrier integrity and recruit peripheral leukocytes. In autoimmune disorders such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders, autoreactive T helper 17 (Th17) and Th1 cells breach the barrier, driving demyelination through pro-inflammatory mediators including interleukin-17 and interferon-γ. Counterbalancing responses involve regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and anti-inflammatory macrophage phenotypes that can foster tissue repair. Dysregulated cytokine networks and aberrant antigen presentation by microglia and infiltrating dendritic cells perpetuate chronic neuroinflammation, contributing to axonal injury and neurodegeneration. Advances in patient-derived cellular models and animal studies have begun to unravel how mediators such as transforming growth factor-β1 and leukaemia inhibitory factor promote neuroprotective glial states, offering new strategies to modulate immune responses and promote regeneration across diverse CNS disorders.

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Immunological Mechanisms in Central Nervous System Disorders publication trend

The graph below shows the total number of articles in immunological mechanisms in central nervous system disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Microglia: Resident immune cells of the CNS that survey the microenvironment, phagocytose debris and present antigens to infiltrating lymphocytes.

Astrocyte: Star-shaped glial cell that supports neuronal function, regulates neurotransmitter levels and contributes to blood–brain barrier maintenance.

Myeloid-derived suppressor cell (MDSC): Immunoregulatory cell derived from the myeloid lineage that suppresses T cell responses and modulates inflammation.

Blood–brain barrier (BBB): Highly selective barrier formed by endothelial cells and astrocyte end-feet that regulates molecular and cellular traffic between blood and CNS.

T helper 17 (Th17) cell: Subset of CD4+ T lymphocytes characterised by interleukin-17 secretion, implicated in autoimmune inflammation and barrier disruption.

Cytokine: Small secreted protein that mediates communication between cells of the immune system, orchestrating inflammatory and regulatory responses.

References

1. iPSC-derived reactive astrocytes from patients with multiple-sclerosis protect cocultured neurons in inflammatory conditions. Journal of Clinical Investigation (2023).
2. Central and peripheral myeloid-derived suppressor cell-like cells are closely related to the clinical severity of multiple sclerosis. Acta Neuropathologica (2023).
3. Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis. Cell Death & Disease (2023).
4. Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications. Mediators of Inflammation (2016).