Neuron-specific SALM5 limits inflammation in the CNS via its interaction with HVEM

Sci Adv. 2016 Apr 8;2(4):e1500637. doi: 10.1126/sciadv.1500637. eCollection 2016 Apr.


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.

Keywords: BBB; CNS; SALM5; immune privilege.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Blood-Brain Barrier / immunology
  • Blood-Brain Barrier / metabolism
  • Cell Adhesion Molecules, Neuronal / immunology
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Central Nervous System / immunology*
  • Central Nervous System / metabolism
  • Inflammation / chemically induced
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Lipopolysaccharides / toxicity
  • Mice
  • Neurons / metabolism
  • Neurons / pathology
  • Receptors, Tumor Necrosis Factor, Member 14 / immunology
  • Receptors, Tumor Necrosis Factor, Member 14 / metabolism*


  • Antibodies, Monoclonal
  • Cell Adhesion Molecules, Neuronal
  • Lipopolysaccharides
  • Receptors, Tumor Necrosis Factor, Member 14
  • SALM5 protein, mouse
  • Tnfrsf14 protein, mouse