An intestinal commensal symbiosis factor controls neuroinflammation via TLR2-mediated CD39 signalling.-猫眼课题宝

DOI：

10.1038/ncomms5432

发表时间：

2014-07-21

期刊：

NATURE COMMUNICATIONS

影响因子：

16.6

通讯作者：

中科院分区：

综合性期刊1区

文献类型：

作者：

Wang, Yan;Telesford, Kiel M.;Ochoa-Reparaz, Javier;Haque-Begum, Sakhina;Christy, Marc;Kasper, Eli J.;Wang, Li;Wu, Yan;Robson, Simon C.;Kasper, Dennis L.;Kasper, Lloyd H.

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118494/?report=classic

The mammalian immune system constitutively senses vast quantities of commensal bacteria and their products through pattern recognition receptors, yet excessive immune reactivity is prevented under homeostasis. Intestinal microbiome can influence host susceptibility to extra-intestine autoimmune disorders. Here we report that polysaccharide A (PSA), a symbiosis factor for human intestinal commensal Bacteroides fragilis, protects against central nervous system demyelination and inflammation during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, through toll-like receptor 2 (TLR2). TLR2 mediates tissue-specific expansion of a critical regulatory CD39+ CD4 T cell subset by PSA. Ablation of CD39 signaling abrogates PSA control of EAE manifestations and inflammatory cytokine responses. Further, CD39 confers immune-regulatory phenotypes to total CD4 T cells and Foxp3+ CD4 Tregs. Importantly, CD39-deficient CD4 T cells show an enhanced capability to drive EAE progression. Our results demonstrate the therapeutic potential and underlying mechanism by which an intestinal symbiont product modulates CNS-targeted demyelination.