信号通过中枢神经系统浸润树突状细胞中的 RIP2 衔接蛋白促进炎症和自身免疫。
Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity.
机构信息
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38104, USA.
出版信息
Immunity. 2011 Jan 28;34(1):75-84. doi: 10.1016/j.immuni.2010.12.015. Epub 2011 Jan 13.
Abstract
Peripheral peptidolgycan (PGN) is present within antigen-presenting cells in the central nervous system (CNS) of multiple sclerosis (MS) patients, possibly playing a role in neuroinflammation. Accordingly, PGN is linked with disease progression in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), but the role of specific PGN-sensing proteins is unknown. Here we report that the progression of EAE was dependent on the intracellular PGN sensors NOD1 and NOD2 and their common downstream adaptor molecule, receptor interacting protein 2 (RIP2; also known as RIPK2 and RICK). We found that RIP2, but not toll-like receptor 2 (TLR2), played a critical role in the activation of CNS-infiltrating dendritic cells. Our results suggest that PGN in the CNS is involved in the pathogenesis of EAE through the activation of infiltrating dendritic cells via NOD1-, NOD2-, and RIP2-mediated pathways.
摘要
外周肽聚糖（PGN）存在于多发性硬化症（MS）患者中枢神经系统（CNS）中的抗原呈递细胞内，可能在神经炎症中发挥作用。因此，PGN 与 MS 的动物模型实验性自身免疫性脑脊髓炎（EAE）中的疾病进展有关，但特定 PGN 感知蛋白的作用尚不清楚。在这里，我们报告 EAE 的进展依赖于细胞内 PGN 传感器 NOD1 和 NOD2 及其共同的下游衔接子分子，受体相互作用蛋白 2（RIP2；也称为 RIPK2 和 RICK）。我们发现 RIP2 而不是 Toll 样受体 2（TLR2）在激活中枢神经系统浸润树突状细胞中发挥关键作用。我们的结果表明，CNS 中的 PGN 通过 NOD1、NOD2 和 RIP2 介导的途径激活浸润的树突状细胞参与 EAE 的发病机制。
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