A Shifting Immune Landscape: ILC Redistribution and Neutrophil Polarization in Vascular Cognitive Impairment and Dementia (VCID)

Vascular cognitive impairment and dementia (VCID) has emerged as a significant factor in cognitive decline, yet the precise mechanisms by which vascular dysfunction triggers innate immune dysregulation remain unclear. This study investigates the influence of VCID on the cerebral innate immune system, specifically examining innate lymphoid cells (ILCs) and neutrophils, which are crucial in neuroinflammation and brain immune regulation.

Utilizing a murine model of VCID resulting from bilateral common carotid artery stenosis (BCAS) in C57BL/6 mice, researchers examined innate immune cell distribution, polarization, and function through flow cytometry and immunofluorescence staining techniques.

The study uncovered a compartment-specific shift in ILC populations, characterized by a decrease in ILC2s in the meninges and an expansion in the choroid plexus. This redistribution was associated with altered cytokine production. Additionally, VCID led to a substantial shift in neutrophil polarization, promoting a pro-inflammatory N1-like phenotype in both the meninges and choroid plexus.

Crucially, immunofluorescence staining of hippocampal brain sections revealed that activated N1-like neutrophils, marked by increased IL-1β and MPO and decreased IL-10, infiltrated the hippocampal parenchyma in VCID. This finding suggests a spatially progressive innate immune response, beginning at the brain's central nervous system borders and extending into brain tissue.

The findings identify a distinct innate immune signature in VCID, comprising compartment-specific ILC redistribution, pro-inflammatory neutrophil polarization at CNS borders, and parenchymal neutrophil infiltration in the hippocampus. These changes may collectively exacerbate neuroinflammation and hasten cognitive decline, suggesting potential therapeutic targets for vascular-related dementia.