title: Neuron-specific SALM5 limits inflammation in the CNS via its interaction with HVEM.
abstract: The central nervous system (CNS) is an immune-privileged organ with the capacity to prevent excessive inflammation. Aside from the blood-brain barrier, active immunosuppressive mechanisms remain largely unknown. We report that a neuron-specific molecule, synaptic adhesion-like molecule 5 (SALM5), is a crucial contributor to CNS immune privilege. We found that SALM5 suppressed lipopolysaccharide-induced inflammatory responses in the CNS and that a SALM-specific monoclonal antibody promoted inflammation in the CNS, and thereby aggravated clinical symptoms of mouse experimental autoimmune encephalomyelitis. In addition, we identified herpes virus entry mediator as a functional receptor that mediates SALM5's suppressive function. Our findings reveal a molecular link between the neuronal system and the immune system, and provide potential therapeutic targets for the control of CNS diseases.
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Augustine
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Broadwater
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: William
authors.initials: W
authors.lastname: Ruff
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Liqun
authors.identifier: 0000-0003-4170-6598
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Gefeng
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Koji
authors.initials: K
authors.lastname: Tamada
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001812:Blood-Brain Barrier / Q000276:immunology / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000276:immunology / Q000378:metabolism*; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D008070:Lipopolysaccharides; D053240:Receptors, Tumor Necrosis Factor, Member 14; C000612989:SALM5 protein, mouse; C506029:Tnfrsf14 protein, mouse
keywords: BBB; CNS; SALM5; immune privilege