An interferon-β-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage

Makoto Inoue, Po Han Chen, Stephen Siecinski, Qi Jing Li, Chunlei Liu, Lawrence Steinman, Simon G. Gregory, Eric Benner, Mari L. Shinohara

Research output: Contribution to journalArticlepeer-review

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-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.

Original languageEnglish (US)
Pages (from-to)1599-1609
Number of pages11
JournalNature Neuroscience
Volume19
Issue number12
DOIs
StatePublished - Dec 1 2016

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'An interferon-β-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage'. Together they form a unique fingerprint.

Cite this