Glycolipid iGb3 feedback amplifies innate immune responses via CD1d reverse signaling

查看全文 作　　者：Xingguang [1]Liu;Peng [1,2]Zhang;Yunkai [1]Zhang;Zheng [3]Wang;Sheng [1]Xu;Yingke [1]Li;Wanwan [4]Huai;Qingqing [1]Zhou;Xiang [1]Chen;Xi [4]Chen;Nan [1]Li;Peng [5]Wang;Yunsen [3]Li;Xuetao [1,4,6,7]Cao

机构地区：[1]National Key Laboratory of Medical Immunology & Institute of Immunology,Second Military Medical University,Shanghai 200433,China;[2]Department of Haematology,General Hospital of Southern Theater Command,Guangzhou 510000,China;[3]Laboratory of Cellular and Molecular Tumor Immunology,Institutes of Biology and Medical Sciences,Jiangsu Laboratory of Infection Immunity,Soochow University,Suzhou 215123,China;[4]Institute of Immunology,Zhejiang University School of Medicine,Hangzhou 310058,China;[5]College of Pharmacy,Nankai University,Tianjin 30071,China;[6]College of Life Science,Nankai University,Tianjin 30071,China;[7]Department of Immunology & Center for Immunotherapy,Institute of Basic Medical Sciences,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100005,China

出　　处：《Cell Research》索引2019年第29卷第1期,共12页

基　　金：the National Key Basic Research Program of China (2015CB964403 to X.C.);the National Natural Science Foundation of China (81788101 to X.C.,31570871 to X.L.,31770970 to X.L., 81600182 to P.Z.,81571543 to Y.L.);CAMS Innovation Fund for Medical Sciences (2016-12M-1-003 to X.C.);'Shuguang Program'of Shanghai Education Development Foundation and Shanghai Municipal Education Commission (18SG33 to X.L.). 摘　　要：The cross-talk between cellular lipid metabolism and the innate immune responses remains obscure. In addition to presenting lipid antigens to Natural Killer T-cells (NKT cells), the Cluster of Differentiation 1D Glycoprotein (CD1d) might mediate reverse signaling in antigen-presenting cells (APCs). Here we found CD1d deficiency attenuated Toll-like receptor (TLR)-triggered inflammatory innate responses in macrophages and dendritic cells, protecting mice from endotoxin shock. TLR activation in macrophages induced metabolic changes of glycosphingolipids (GSLs), among which glycolipid isoglobotrihexosylceramide (iGb3) was rapidly produced. The endogenously generated iGb3 bound CD1d in endosomal compartments and then synergized with the initially activated TLR signal to induce Tyr332 phosphorylation of CD1d intracellular domain. This led to the recruitment and activation of proline-rich tyrosine kinase 2 (Pyk2). Pyk2 interacted with IκB kinase β (IKKβ) and TANK-binding kinase 1 (TBK1), and enhanced tyrosine phosphorylation of Tyr188/199 of IKKβ and Tyr179 of TBK1 and thus, their activation to promote full activation of TLR signaling. Thus, intracellular CD1d reverse signaling, triggered by endogenous iGb3, amplifies inflammatory innate responses in APCs. Our findings identify a non-canonical function of CD1d reverse signaling activated by lipid metabolite in the innate immune response. 关键词：Natural Killer T-CELLS (NKT cells) antigen-presenting CELLS (APCs)

相关文献

参考文献（56）
引证文献（1）
耦合文献（104）

参考文献(56)

引证文献(1)

耦合文献(104)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

Glycolipid iGb3 feedback amplifies innate immune responses via CD1d reverse signaling

参考文献(56)

引证文献(1)

耦合文献(104)

用户提示