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An interferon-beta-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage NATURE NEUROSCIENCE Inoue, M., Chen, P., Siecinski, S., Li, Q., Liu, C., Steinman, L., Gregory, S. G., Benners, E., Shinohara, M. L. 2016; 19 (12): 1599-1609

Abstract

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

View details for DOI 10.1038/nn.4421

View details for Web of Science ID 000389011900019