Fig. 2

The roles of NK cells in CNS diseases. In EAE, NK cells play a pivotal role in curtailing excessive autoimmune responses by eliminating autoreactive T cells and activated microglia, and fostering anti-inflammatory astrocytes. The malfunction of NK cells in their immunoregulatory roles may accelerate the progression of the disease. Conversely, NK cells also lyse neural stem cells and participate in demyelination, resulting in brain damage. During normal aging, NK cells accumulate in aged dentate gyrus, where they engage in elimination of senescent neuroblasts, consequently impairing neurogenesis. The roles of NK cells in neurodegenerative diseases remain elusive. NK cells may serve as scavengers of α-synuclein aggregates in PD, but concurrently exacerbate ALS by causing neuronal damage and creating inflammatory milieu. During stroke onset, NK cells infiltrate into brain parenchyma and kill hypoxic neurons and endothelia cells, thereby aggravating secondary brain injury. In CNS infectious diseases, NK cells exert positive effects in combating infections, but their enhanced cytotoxicity and cytokine production may yield adverse consequences. Treatment of cerebral malaria with IL-15 successfully improves outcomes of the disease by activating NK cells to modulate deleterious responses of pathogenic T cells. (Created with BioRender.com)