Interferon-β therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome.

Published online

Journal Article

Interferon-β (IFN-β) is widely used to treat multiple sclerosis (MS), and its efficacy was demonstrated in the setting of experimental autoimmune encephalomyelitis (EAE), an animal model of MS; however, IFN-β is not effective in treating all cases of MS. Here, we demonstrate that signaling by IFNAR (the shared receptor for IFN-α and IFN-β) on macrophages inhibits activation of Rac1 and the generation of reactive oxygen species (ROS) through suppressor of cytokine signaling 1 (SOCS1). The inhibition of Rac1 activation and ROS generation suppressed the activity of the Nod-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome, which resulted in attenuated EAE pathogenicity. We further found that two subsets of EAE could be defined on the basis of their dependency on the NLRP3 inflammasome and that IFN-β was not an effective therapy when EAE was induced in an NLRP3 inflammasome-independent fashion. Thus, our study demonstrates a previously uncharacterized signaling pathway that is involved in the suppression of EAE by IFN-β and characterizes NLRP3-independent EAE, which cannot be treated with IFN-β.

Full Text

Duke Authors

Cited Authors

  • Inoue, M; Williams, KL; Oliver, T; Vandenabeele, P; Rajan, JV; Miao, EA; Shinohara, ML

Published Date

  • May 22, 2012

Published In

Volume / Issue

  • 5 / 225

Start / End Page

  • ra38 -

PubMed ID

  • 22623753

Pubmed Central ID

  • 22623753

Electronic International Standard Serial Number (EISSN)

  • 1937-9145

Digital Object Identifier (DOI)

  • 10.1126/scisignal.2002767

Language

  • eng

Conference Location

  • United States