Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of the central nervous system (CNS). A major component of the immunopathology of MS is the T cell-driven inflammatory attack from the peripheral immune system towards the CNS.
A recently published review article (https://doi.org/10.2478/rrlm-2020-0005) showed that T helper (Th) 17 lymphocytes appear to be one of the main cellular players in MS immunopathology. One of the major functions described for Th17 cells is the upregulation of pro-inflammatory cytokines, such as IL-17 at the level of peripheral and CNS inflammation.
In MS patients, Th17 cells have been shown to promote meningeal microenvironmental re-modelling, by inducing the production of proinflammatory cytokines, chemokines and various extracellular matrix proteins. This has a deleterious effect in MS evolution, leading to brain inflammation with sustained myelin and axonal damage.
The direct interaction between myelin oligodendrocyte glycoprotein-specific Th17 with neuronal cells induces demyelinating lesions and secondary extensive axonal damage. Th17 cells that produce IL-17 have also been shown to play a pivotal role in the formation of aggregates, known as ectopic lymphoid structures (ELS).
ELS stimulate cortical demyelination and axonal atrophy that are associated with the progression of neurological dysfunction in MS cases. IL-17 also displays crucial inhibitory effects on the in vitro development of oligodendrocyte lineage cells, by reducing their survivability through the stimulation of the tumour necrosis factor (TNF)-α-mediated cell death cascade. This furthermore induces oligodendrocyte loss through apoptosis:
Due to their role in preventing remyelination and their direct neurotoxic effect, Th17 cells represent an important connection between neuroinflammation and neurodegeneration in a devastating disease like MS. A number of experimental studies have already indicated that blocking IL-17 signalling decreased the formation of ELS.
At Synexa Life Sciences, we are developing a three-dimensional in vitro cellular model, that will allow for the assessment of the influence of specific immune cells, and their secreted cytokines on neuronal cell myelin and viability. In addition, Synexa has a comprehensive portfolio of validated biomarker assays to measure cytokines, chemokines and other inflammatory markers and neurotransmitters. Together, these may provide valuable insight into methods of action and therapeutic potential of drug candidates.
