" Investigating the importance of inflammasome activation locally in microglia in the pathology of MS "
Chronic inflammation contributes to various diseases, including multiple sclerosis (MS), the most common inflammatory disease of the central nervous system (CNS). Our research aims to better understand the role of microglia, a particular brain cell type, in CNS inflammation and the pathology of MS. Microglia are involved in the activation of so-called ‘inflammasomes’, cellular protein complexes responsible for the production of important inflammatory mediators in the brain.
By studying the molecular mechanisms behind microglia inflammasome activation, we hope to contribute to a better knowledge on MS which may help in the development of better therapies.
the scientific project
Microglial cells are the resident mononuclear phagocytes of the central nervous system (CNS) and have a functional role in both immune defense and CNS maintenance. These cells may however also acquire a detrimental pro-inflammatory phenotype that actively contributes to the chronicity of inflammatory brain diseases, including the neuroinflammatory disease multiple sclerosis (MS). Accordingly, inhibiting the pro-inflammatory status of microglia may suppress disease development and help to treat MS. However, to achieve this, a better knowledge about the molecular mechanisms controlling microglia activation is absolutely needed.
One of the mechanisms crucially controlling inflammatory reactions is the activation of inflammasomes, cytosolic multi-protein complexes responsible for the production of the inflammatory cytokines interleukin-1b (IL-1b) and IL-18, and for inducing pyroptosis, a lytic form of cell death provoking inflammatory reactions. Although inflammasome activation has been implicated in many infectious, immune and inflammatory processes, still very little is known about their specific contribution to CNS inflammation and MS pathology. With our project we aim to contribute to a better insight in the specific role of inflammasomes and their regulation in microglia in the context of MS.
