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

(2012) SCIENCE SIGNALING. 5(225).
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Abstract
Interferon-beta (IFN-beta) 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-beta is not effective in treating all cases of MS. Here, we demonstrate that signaling by IFNAR (the shared receptor for IFN-alpha and IFN-beta) 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-beta 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-beta and characterizes NLRP3-independent EAE, which cannot be treated with IFN-beta.
Keywords
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, MULTIPLE-SCLEROSIS, CENTRAL-NERVOUS-SYSTEM, NALP3 INFLAMMASOME, DENDRITIC CELLS, ACTIVATION, EXPRESSION, CASPASE-1, MECHANISM, RESPONSES

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Chicago
Inoue, Makoto, Kristi L Williams, Timothy Oliver, Peter Vandenabeele, Jayant V Rajan, Edward A Miao, and Mari L Shinohara. 2012. “Interferon-β Therapy Against EAE Is Effective Only When Development of the Disease Depends on the NLRP3 Inflammasome.” Science Signaling 5 (225).
APA
Inoue, M., Williams, K. L., Oliver, T., Vandenabeele, P., Rajan, J. V., Miao, E. A., & Shinohara, M. L. (2012). Interferon-β therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome. SCIENCE SIGNALING, 5(225).
Vancouver
1.
Inoue M, Williams KL, Oliver T, Vandenabeele P, Rajan JV, Miao EA, et al. Interferon-β therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome. SCIENCE SIGNALING. 2012;5(225).
MLA
Inoue, Makoto, Kristi L Williams, Timothy Oliver, et al. “Interferon-β Therapy Against EAE Is Effective Only When Development of the Disease Depends on the NLRP3 Inflammasome.” SCIENCE SIGNALING 5.225 (2012): n. pag. Print.
@article{2153283,
  abstract     = {Interferon-beta (IFN-beta) 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-beta is not effective in treating all cases of MS. Here, we demonstrate that signaling by IFNAR (the shared receptor for IFN-alpha and IFN-beta) 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-beta 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-beta and characterizes NLRP3-independent EAE, which cannot be treated with IFN-beta.},
  articleno    = {ra38},
  author       = {Inoue, Makoto and Williams, Kristi L and Oliver, Timothy and Vandenabeele, Peter and Rajan, Jayant V and Miao, Edward A and Shinohara, Mari L},
  issn         = {1937-9145},
  journal      = {SCIENCE SIGNALING},
  keyword      = {EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS,MULTIPLE-SCLEROSIS,CENTRAL-NERVOUS-SYSTEM,NALP3 INFLAMMASOME,DENDRITIC CELLS,ACTIVATION,EXPRESSION,CASPASE-1,MECHANISM,RESPONSES},
  language     = {eng},
  number       = {225},
  pages        = {8},
  title        = {Interferon-\ensuremath{\beta} therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome},
  url          = {http://dx.doi.org/10.1126/scisignal.2002767},
  volume       = {5},
  year         = {2012},
}

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