학술논문
An interferon-[beta]-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage
encephalomyelitis
NACHT, LRR and PYD domains-containing protein 3
encephalomyelitis
NACHT, LRR and PYD domains-containing protein 3
Document Type
Report
Author
Source
Nature Neuroscience. December 2016, Vol. 19 Issue 12, p1599, 11 p.
Subject
Language
English
ISSN
1097-6256
Abstract
Author(s): Makoto Inoue [1, 2]; Po-han Chen [3]; Stephen Siecinski [4]; Qi-jing Li [1]; Chunlei Liu [5, 6]; Lawrence Steinman [7]; Simon G Gregory [4]; Eric Benner [8]; Mari L [...]
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] (IFN[beta])-resistant EAE (termed type B EAE), whereas EAE induced by weak activation of innate immunity requires the NLRP3 inflammasome and is sensitive to IFN[beta] treatment. Instead, an alternative inflammatory mechanism, including membrane-bound lymphotoxin-[beta] receptor (LT[beta]R) 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 IFN[beta]-resistant multiple sclerosis. Remission was minimal in type B EAE due to neuronal damages induced by semaphorin 6B upregulation on CD4[sup.+] T cells. Our data reveal a new inflammatory mechanism by which an IFN[beta]-resistant EAE subtype develops.
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] (IFN[beta])-resistant EAE (termed type B EAE), whereas EAE induced by weak activation of innate immunity requires the NLRP3 inflammasome and is sensitive to IFN[beta] treatment. Instead, an alternative inflammatory mechanism, including membrane-bound lymphotoxin-[beta] receptor (LT[beta]R) 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 IFN[beta]-resistant multiple sclerosis. Remission was minimal in type B EAE due to neuronal damages induced by semaphorin 6B upregulation on CD4[sup.+] T cells. Our data reveal a new inflammatory mechanism by which an IFN[beta]-resistant EAE subtype develops.