Innate immunity in the brain: ILC2s as modulators of CNS disorders

Innate lymphoid cells (ILCs), particularly group 2 innate lymphoid cells (ILC2s), have emerged as crucial players in central nervous system (CNS) homeostasis and pathology. This review explores the multifaceted roles of ILC2s across various CNS disorders, highlighting their potential as therapeutic targets. ILC2s, enriched in brain barriers like the meninges and choroid plexus, respond to alarmins such as IL-33 and IL-25, orchestrating immune responses through producing type 2 cytokines including IL-5 and IL-13. In aging brains, ILC2s demonstrate remarkable adaptability, resisting senescence, and maintaining self-renewal capacity. However, in Alzheimer's disease, ILC2s show numerical and functional deficits, potentially exacerbating neuroinflammation and cognitive decline. This review synthesizes recent findings on ILC2 involvement in CNS injuries, infections, stroke, ischemia, and their influence on behavior and cognition. We examine how ILC2s modulate neuroinflammation, promote tissue repair, and impact cognitive outcomes across these conditions. By integrating current research, we aim to provide a comprehensive understanding of ILC2 functions in CNS disorders and their potential as targets for novel therapeutic strategies.