title: Central nervous system (CNS)-resident natural killer cells suppress Th17 responses and CNS autoimmune pathology.
abstract: Natural killer (NK) cells of the innate immune system can profoundly impact the development of adaptive immune responses. Inflammatory and autoimmune responses in anatomical locations such as the central nervous system (CNS) differ substantially from those found in peripheral organs. We show in a mouse model of multiple sclerosis that NK cell enrichment results in disease amelioration, whereas selective blockade of NK cell homing to the CNS results in disease exacerbation. Importantly, the effects of NK cells on CNS pathology were dependent on the activity of CNS-resident, but not peripheral, NK cells. This activity of CNS-resident NK cells involved interactions with microglia and suppression of myelin-reactive Th17 cells. Our studies suggest an organ-specific activity of NK cells on the magnitude of CNS inflammation, providing potential new targets for therapeutic intervention.
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
authors.forename: Ruolan
authors.initials: R
authors.lastname: Liu
authors.forename: Wenhua
authors.initials: W
authors.lastname: Piao
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Vollmer
authors.forename: Denise I
authors.initials: DI
authors.lastname: Campagnolo
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.forename: Antonio
authors.initials: A
authors.lastname: La Cava
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002465:Cell Movement; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D007108:Immune Tolerance; D020381:Interleukin-17 / Q000172:deficiency / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D007376:Interleukin-2