Immunological Dynamics in Multiple Sclerosis Pathogenesis

Multiple sclerosis (MS) is a complex autoimmune disorder in which aberrant immune responses target the myelin sheath of central nervous system axons, leading to neuroinflammation, demyelination and neurodegeneration. A critical interplay exists between adaptive immune cells—CD4+ T helper subsets, particularly Th17 cells, and autoreactive B cells—and innate effectors such as macrophages and microglia. Th17 cells secrete interleukin-17 and other pro-inflammatory cytokines that recruit and activate B cells, which in turn present antigen, produce cytokines and generate autoantibodies. Activated microglia and infiltrating macrophages amplify tissue damage via reactive oxygen species and inflammatory mediators. Counterbalancing these processes, regulatory T cell and B cell subsets release interleukin-10 and other anti-inflammatory factors, shaping the transition from relapsing–remitting phases to progressive disability. Understanding these dynamic cellular and molecular networks is guiding the development of precision immunotherapies aimed at restoring immune tolerance and halting disease progression.

Research from Nature Portfolio

Recent studies have demonstrated that myelin-specific B cells can amplify CNS autoimmunity through an interleukin-23-dependent axis. In experimental models, B cells reactive to myelin oligodendrocyte glycoprotein foster the expansion and maintenance of Th17 cells and accumulate alongside a PD-1+CXCR5– T peripheral helper-like subset in both the meninges and parenchyma. These cellular aggregates produce reactive oxygen species and sustain local inflammation, while targeted blockade of the IL-23p19 subunit reduces cell infiltration and ameliorates disease severity. These findings underscore the importance of B–T cell crosstalk in driving chronic CNS inflammation.

Immunological Dynamics in Multiple Sclerosis Pathogenesis publication trend

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

Technical terms

Th17 cells: A subset of CD4+ T helper cells producing interleukin-17, central to autoimmune inflammation.

T peripheral helper (Tph) cells: A non-follicular T cell subset that supports B cell activation and antibody production in peripheral tissues.

IL-23: An interleukin that maintains and expands Th17 cells, promoting chronic inflammation.

MHC class I: Cell surface proteins presenting endogenous peptides to CD8+ T cells, enabling targeted cytotoxic responses.

Regulatory B cells (Breg): B cell subsets that secrete anti-inflammatory cytokines such as interleukin-10 to suppress immune-mediated damage.

Experimental autoimmune encephalomyelitis (EAE): A rodent model of MS that reproduces key features of CNS demyelination and inflammation.

References

1. Myelin-reactive B cells exacerbate CD4+ T cell-driven CNS autoimmunity in an IL-23-dependent manner. Nature Communications (2024).
2. CD8+ T cells recognizing a neuron-restricted antigen injure axons in a model of multiple sclerosis. Journal of Clinical Investigation (2023).
3. IL-10-providing B cells govern pro-inflammatory activity of macrophages and microglia in CNS autoimmunity. Acta Neuropathologica (2023).