Investigating microglia heterogeneity in the central nervous system at steady state and under inflammatory or neurodegenerative diseases
As the only parenchymal-resident immune cells of the central nervous system (CNS), microglia act as critical effectors and regulators of changes in the CNS during development and adult homeostasis. Their ontogeny, together with the absence of turnover from the periphery and the exceptional environment of the CNS, make microglia a unique immune cell population. By sensing any disruption of the CNS homeostasis, microglia rapidly change their gene expression programs and functional profiles. Microglia coordinate immune responses between the periphery and the CNS as they perceive and propagate inflammatory signals initiated outside the CNS. A multitude of signals received from the CNS environment as well as from the periphery induce microglial responses towards phenotypes that ultimately may support or harm neuronal health. However, whether all microglial cells uniformly react to a specific perturbation is not entirely understood.
To elucidate the heterogeneity of microglia at steady state as well as under inflammatory and neurodegenerative processes, we take advantage of mouse models of human diseases and apply state-of-the-art techniques, including multicolour flow cytometry and single-cell RNA-sequencing, to identify distinct programs associated to specific neurological diseases.
Understanding the specific molecular triggers and the subsequent heterogeneous genetic programs defining microglia under homeostatic, inflammatory, and neurodegenerative conditions is a critical step to uncover the multifaceted nature of microglia, thus opening new windows to design novel therapeutic strategies to restore, for example, efficient inflammatory immune responses in CNS diseases.
This project is supported by the Luxembourg National Research Fund (AFR 6916713), the Luxembourg Institute of Health & Luxembourg Centre for Systems Biomedicine (MIGLISYS), the Rotary Clubs of Luxembourg (Espoir en Tête®) and the Fondation du Pélican de Mie and Pierre Hippert-Faber Under the Aegis of Fondation de Luxembourg.