title: Ischemic neurons recruit natural killer cells that accelerate brain infarction.
abstract: Brain ischemia and reperfusion activate the immune system. The abrupt development of brain ischemic lesions suggests that innate immune cells may shape the outcome of stroke. Natural killer (NK) cells are innate lymphocytes that can be swiftly mobilized during the earliest phases of immune responses, but their role during stroke remains unknown. Herein, we found that NK cells infiltrated the ischemic lesions of the human brain. In a mouse model of cerebral ischemia, ischemic neuron-derived fractalkine recruited NK cells, which subsequently determined the size of brain lesions in a T and B cell-independent manner. NK cell-mediated exacerbation of brain infarction occurred rapidly after ischemia via the disruption of NK cell tolerance, augmenting local inflammation and neuronal hyperactivity. Therefore, NK cells catalyzed neuronal death in the ischemic brain.
authors.affiliation: Department of Neurology, Key Laboratory of Neurorepair and Regeneration, Tianjin and Ministry of Education and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Jun-Xiang
authors.initials: JX
authors.lastname: Yin
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Bai
authors.forename: Rulong
authors.initials: R
authors.lastname: Shen
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Jieli
authors.initials: J
authors.lastname: Chen
authors.forename: Antonio
authors.initials: A
authors.lastname: La Cava
authors.forename: Jennifer
authors.initials: J
authors.lastname: Poursine-Laurent
authors.forename: Wayne
authors.initials: W
authors.lastname: Yokoyama
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000276:immunology*; D020520:Brain Infarction / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications / Q000276:immunology*; D054428:Chemokine CX3CL1 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D020521:Stroke / Q000150:complications / Q000276:immunology*
chemical_list: D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse
keywords: innate immunity; ischemic stroke; middle cerebral artery occlusion