Neuroinflammatory Mechanisms in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterised by immune‐mediated damage to myelin sheaths, axons and neurons. A cascade of events begins with disruption of the blood–brain barrier, permitting infiltration of autoreactive lymphocytes, monocytes and other myeloid cells into the parenchyma. Resident microglia and astrocytes amplify this response by secreting pro‐inflammatory cytokines and chemokines that recruit further immune cells and sustain local inflammation. Antigen presentation by dendritic cells and macrophages drives differentiation of T helper‐1 and T helper‐17 cells, whose effector molecules induce oligodendrocyte injury and demyelination. B cells contribute via antibody production, cytokine release and formation of ectopic lymphoid structures in meninges, which correlates with cortical pathology. Emerging evidence implicates non‐immune factors—such as coagulation proteins and lipid mediators—in modulating neuroinflammation. These molecules can act as danger signals, promoting antigen presentation or driving necroptotic pathways in neurons. The interplay between adaptive and innate immunity, vascular dysfunction and glial responses underpins lesion formation, remyelination failure and progressive neurodegeneration. A deeper mechanistic understanding aims to inform targeted therapies that restore barrier integrity, modulate key signalling cascades and protect neural elements.

Research from Nature Portfolio

Research has revealed that fibrinogen, deposited following blood–brain barrier breach, acts beyond clotting to drive CNS autoimmunity. In experimental models, fibrinogen interacts with CD11b/CD18 on antigen‐presenting cells, inducing a transcriptional programme that enhances myelin‐specific Th1 cell recruitment and activation. This process results in macrophage infiltration, chemokine release and focal demyelination. Genetic or pharmacological depletion of fibrinogen markedly reduces encephalitogenic T‐cell responses and tissue damage, underscoring the coagulation cascade’s dual role in haemostasis and neuroinflammatory amplification.

Neuroinflammatory Mechanisms in Multiple Sclerosis publication trend

The graph below shows the total number of articles in neuroinflammatory mechanisms in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Blood–brain barrier: A selective vascular interface that restricts passage of cells and molecules between blood and CNS.

Demyelination: Loss or damage of the myelin sheath surrounding axons, impairing nerve conduction.

Antigen‐presenting cell: Immune cell (e.g., dendritic cell, macrophage) that displays peptide–MHC complexes to T cells.

Th1 cell: A subtype of CD4+ T helper cell that produces interferon-γ and promotes cell‐mediated immunity.

Necroptosis: Regulated form of cell death driven by RIPK1/RIPK3/MLKL signalling, leading to membrane rupture.

Eicosanoids: Bioactive lipid mediators derived from polyunsaturated fatty acids that modulate inflammation.

References

1. Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation. Nature Communications (2015).
2. T-bet+ CXCR3+ B cells drive hyperreactive B-T cell interactions in multiple sclerosis. Cell Reports Medicine (2025).
3. Arachidonic acid-derived lipid mediators in multiple sclerosis pathogenesis: fueling or dampening disease progression?. Journal of Neuroinflammation (2024).
4. Neuron-specific activation of necroptosis signaling in multiple sclerosis cortical grey matter. Acta Neuropathologica (2021).