Cytosolic RIG-I-like helicases act as negative regulators of sterile inflammation in the CNS

Nat Neurosci. 2011 Dec 4;15(1):98-106. doi: 10.1038/nn.2964.


The action of cytosolic RIG-I-like helicases (RLHs) in the CNS during autoimmunity is largely unknown. Using a mouse model of multiple sclerosis, we found that mice lacking the RLH adaptor IPS-1 developed exacerbated disease that was accompanied by markedly higher inflammation, increased axonal damage and elevated demyelination with increased encephalitogenic immune responses. Furthermore, activation of RLH ligands such as 5'-triphosphate RNA oligonucleotides decreased CNS inflammation and improved clinical signs of disease. RLH stimulation repressed the maintenance and expansion of committed T(H)1 and T(H)17 cells, whereas T-cell differentiation was not altered. Notably, T(H)1 and T(H)17 suppression required type I interferon receptor engagement on dendritic cells, but not on macrophages or microglia. These results identify RLHs as negative regulators of T(H)1 and T(H)17 responses in the CNS, demonstrate a protective role of the RLH pathway for brain inflammation, and establish oligonucleotide ligands of RLHs as potential therapeutics for the treatment of multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity / immunology
  • Cell Differentiation / immunology
  • Cell Survival / immunology
  • Central Nervous System / enzymology*
  • Central Nervous System / immunology*
  • Central Nervous System / metabolism
  • Cytosol / enzymology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / enzymology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Mice
  • RNA Helicases / metabolism*
  • Receptor, Interferon alpha-beta / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism


  • Receptor, Interferon alpha-beta
  • RNA Helicases