Interferon Resistant EAE

Inoue M, Chen PH, Siecinski S, Li QJ, Liu C, Steinman L, Gregory SG, Benner E, Shinohara ML. An interferon-β-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage. Nat Neurosci. 2016 Nov 7. doi: 10.1038/nn.4421. [Epub ahead of print]

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-β (IFNβ)-resistant EAE (termed type B EAE), whereas EAE induced by weak activation of innate immunity requires the NLRP3 inflammasome and is sensitive to IFNβ treatment. Instead, an alternative inflammatory mechanism, including membrane-bound lymphotoxin-β receptor (LTβR) 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 IFNβ-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 IFNβ-resistant EAE subtype develops.

I don't comment on that many EAE, but try to do them when they are in big journals I thought I was going to try an explain this one, but to be honest it would take me hours to do it justice and then you would say "so what." So we have interferon resistant EAE do we have interferon resistant MS?...Seemingly so. 

I did write to the authors to ask them if they had data when they said they gave gel food for the beasties to limit weight loss. They said they didn't actually have any data. They just did it because they were told to do it by their vet. Funny that..because in many cases C57BL/6 can get EAE without much weight loss anyway.

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