| First Author | Inoue M | Year | 2012 |
| Journal | Sci Signal | Volume | 5 |
| Issue | 225 | Pages | ra38 |
| PubMed ID | 22623753 | Mgi Jnum | J:259478 |
| Mgi Id | MGI:6141296 | Doi | 10.1126/scisignal.2002767 |
| Citation | Inoue M, et al. (2012) Interferon-beta therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome. Sci Signal 5(225):ra38 |
| abstractText | 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. |
