Past infections increase the likelihood to develop intestinal, hepatic and neurodegenerative diseases, suggesting the existence of a tissue-specific immune memory. We hypothesize that the immune memory of tissues is largely contained within self-maintaining tissue-resident macrophages, that are
long-lived and very plastic. We discovered that the self-maintenance and tissue-specific identities of resident macrophages are instructed by micro-environmental niches. MacNicheMemo will investigate whether: (i) resident macrophages and their niche "remember" previous inflammatory episodes, (ii) this "macrophage niche memory" affects the homeostatic function of macrophages and their response to subsequent insults, (iii) resetting the homeostatic cell-cell circuits within the macrophage niche prevents macrophage dysregulation and disease susceptibility. For this we
combine leading macrophage biology expertise with front-line single-cell multi-omics technologies.