Immune interface of the gut in brain diseases

초록

Immune interface of the gut in brain diseases Youngshik Choe Developmental Disorders & Rare Diseases Research Group, Korea Brain Research Institute The central nervous system (CNS) is an immune-specialized organ safeguarded by innate immune mechanisms, including parenchymal microglia and border-associated macrophages (BAMs) residing in the perivascular, meningeal, and choroid plexus niches. These brain-resident immune cells maintain homeostasis and respond dynamically to pathological conditions such as Alzheimer’s disease and neurodevelopmental disorders. In brain disorders, immune compartments, particularly the meninges, undergo profound transcriptomic and proteomic remodeling. The meninges serve as a critical hub where CNS-resident innate immune cells interact with adaptive immune cells and peripheral immune influences, including those derived from the gut immune system. To investigate these interactions at high resolution, we employed a spatial single-cell proteomics approach integrated with spatial transcriptomics. This strategy enabled unprecedented deep proteomic profiling of individual immune cells, including dural BAMs and microglia, across distinct brain disease models. The spatial immune map generated by this approach provides a framework for understanding how resident macrophages orchestrate neuroimmune interactions across CNS and peripheral compartments. Ongoing integration with single-cell RNA sequencing and spatial transcriptomics will further elucidate the spatiotemporal dynamics of immune cell states in health and disease.