| First Author | Inoue M | Year | 2016 |
| Journal | Nat Neurosci | Volume | 19 |
| Issue | 12 | Pages | 1599-1609 |
| PubMed ID | 27820602 | Mgi Jnum | J:238271 |
| Mgi Id | MGI:5818983 | Doi | 10.1038/nn.4421 |
| Citation | Inoue M, et al. (2016) An interferon-beta-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage. Nat Neurosci 19(12):1599-1609 |
| abstractText | Inflammation induced by innate immunity influences the development of T cell-mediated autoimmunity in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). We found that strong activation of innate immunity induced Nod-like receptor protein 3 (NLRP3) inflammasome-independent and interferon-beta (IFNbeta)-resistant EAE (termed type B EAE), whereas EAE induced by weak activation of innate immunity requires the NLRP3 inflammasome and is sensitive to IFNbeta treatment. Instead, an alternative inflammatory mechanism, including membrane-bound lymphotoxin-beta receptor (LTbetaR) and CXC chemokine receptor 2 (CXCR2), is involved in type B EAE development, and type B EAE is ameliorated by antagonizing these receptors. Relative expression of Ltbr and Cxcr2 genes was indeed enhanced in patients with IFNbeta-resistant multiple sclerosis. Remission was minimal in type B EAE due to neuronal damages induced by semaphorin 6B upregulation on CD4+ T cells. Our data reveal a new inflammatory mechanism by which an IFNbeta-resistant EAE subtype develops. |
