Descripción del proyecto
Una visión holística de los macrófagos del encéfalo
La microglía son las células inmunitarias innatas más prominentes y longevas del sistema nervioso central. Aparecen en las primeras fases del desarrollo en el saco vitelino y su función principal es combatir agentes patógenos y eliminar residuos celulares para mantener la homeostasis tisular. El objetivo del proyecto MADEFUN, financiado con fondos europeos, es determinar cómo se diferencian en el encéfalo los distintos tipos de macrófagos y cómo afectan al desarrollo encefálico. Además de determinar su distribución espaciotemporal, los investigadores estudiarán la implicación de los macrófagos en neuropatologías como la neurodegeneración y la inflamación.
Objetivo
Macrophages are part of the mononuclear phagocyte system and play critical roles in innate immune responses. They further exert crucial organ-specific functions to warrant tissue homeostasis. Most macrophages are long-lived and derive from embryonic precursors. The central nervous system (CNS) contains several macrophage populations, of which microglia are the most prominent and abundant population residing in the CNS parenchyma. Besides being implicated in CNS pathologies, microglia guide neuronal development, are critical for neurogenesis and contribute to the maintenance of tissue homeostasis. At the interface between the brain and the periphery reside choroid plexus, perivascular and meningeal macrophages (‘border-associated’ macrophages, BAMs). While they mostly also originate from embryonic precursors, the differentiation cues and their specific roles in development and in health and disease are poorly understood. Here we will delineate the spatiotemporal emergence of BAMs and microglia, the impact of the local microenvironment on their phenotype and function, and their role in brain development. We will further analyze the role of BAMs and microglia in physiological and neuropathological conditions (neurodegeneration, CNS infection and inflammation). We have recently described a novel ‘microglia-specific’ conditional mouse and we are currently establishing an inducible system to specifically manipulate BAMs. We will use these to genetically intervene in different cytokine signaling pathways in combination with fate-mapping in vivo. The proposed research project will provide a deeper insight into microglia and BAM biology and their functional specializations at different stages of life.
Ámbito científico
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Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
8006 Zurich
Suiza