Neural stem cells sustain natural killer cells that dictate recovery from brain inflammation

Natural killer (NK) cells are retained and reside in the vicinity of neural stem cells (NSCs) in the brain subventricular zone during the chronic phase of multiple sclerosis in humans and its animal model in mice. In this study, the authors show that these NK cells limit NSCs' reparative capacity following brain inflammation, while NSCs promote NK survival via an interleukin-15-dependent mechanism. Recovery from organ-specific autoimmune diseases largely relies on the mobilization of endogenous repair mechanisms and local factors that control them. Natural killer (NK) cells are swiftly mobilized to organs targeted by autoimmunity and typically undergo numerical contraction when inflammation wanes. We report the unexpected finding that NK cells are retained in the brain subventricular zone (SVZ) during the chronic phase of multiple sclerosis in humans and its animal model in mice. These NK cells were found preferentially in close proximity to SVZ neural stem cells (NSCs) that produce interleukin-15 and sustain functionally competent NK cells. Moreover, NK cells limited the reparative capacity of NSCs following brain inflammation. These findings reveal that reciprocal interactions between NSCs and NK cells regulate neurorepair.