High doses of α-galactosylceramide potentiate experimental autoimmune encephalomyelitis by directly enhancing Th17 response  

作　　者：Gaochao Qian Xia Qin Ying Qin Zang Baoxue Ge Taylor B Guo Bing Wan Lei Fang Jingwu Z Zhang 

机构地区：[1]Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, 280 South Chong Qing Road, Shanghai 200025, China [2]Institute for Nutrtional Sciences, Shanghai Institute for Biological Sciences, Graduate School of CAS, Chinese Academy of Sciences, 319 Yue Yang Road, Shanghai 200031, China [3]Institute of Health Sciences, Shanghai Institute for Biological Sciences, Graduate School of CAS, Chinese Academy of Sciences, 319 Yue Yang Road, Shanghai 200031, China

出　　处：《Cell Research》2010年第4期480-491,共12页细胞研究（英文版）

摘　　要：α-Galactosylceramide （u-GC） is widely known to activate invariant natural killer T （iNKT） cells to suppress my- elin antigen-specific Thl responses, protecting susceptible mice against experimental antoimmune encephalomyelitis 0EAE）. Here, we demonstrate an unexpected finding that high doses of α-GC exacerbated, rather than ameliorated, EAE. Similar results were observed when MOG35.ss-specific T cells treated with high-dose α-GC were transferred into naive syngeneic recipient mice. Further study showed that high doses of a-GC directly enhance the Thl7 and Thl re- sponse by activation of CD4＋CD44＋ memory T cells through phosphorylation of STAT3 and activation of NF-kB. Un- like the activation of iNKT cells by low doses of a-GC, high doses of a-GC directly interacted with CDld expressed on T ceils and activated Thl7 and Thl cells. Furthermore, antigen-presenting cells （APCs） predominantly express CDldl, whereas the majority of CD4~ T cells express CDld2. Knockdown of CDldl or CDld2 gene expression by RNAi interfered with the activation of iNKT or Thl7/Thl cells, respectively. Therefore, α-GC treatment could im- prove or worsen EAE by engaging either APCs or Thl7/Thl cells depending on the dose used.

关 键 词：α-GC experimental autoimmune encephalomyelitis IL-17 

分 类 号：Q25[生物学—细胞生物学] TN16[电子电信—物理电子学]