Brain CD4 T cells and their influence over microglial homeostasis (360G-Wellcome-222442_A_21_Z)

Microglia are the main immunological cell of the brain. These residential cells possess both immunological and neurodevelopmental functions, and have pathological roles during age- and injury-associated dementia. We recently characterised a new addition to the neuroimmunological landscape: transiently- resident brain CD4 T cells. Brain T cells are required to trigger the post- natal differentiation of foetal microglia, licensing their neurodevelopmental functions. Much remains unknown about potential further interactions between brain CD4 T cells and microglia. We have adapted cutting-edge technology to enable the parallel study of brain CD4 T cells and microglia. First, will use an adapted flow-based ProCode approach to unravel the molecular control over CD4 T cell entry to the brain and acquisition of the residential phenotype. Second, we have developed a novel genetic tool for competitive chimeric analysis, allowing us to study microglia niche-sensing and the role of interaction with CD4 T cells on microgliosis. Third, we will single cell lineage tracing to dissect the clonal evolution of microglia, and the influence of CD4 T cell interaction on microglial clonal dominance during ageing and following traumatic brain injury. The results will generate new insight into neuroimmune inter-cellular dynamics, and will validate new tools with broad applicability to biomedical sciences.