Central nervous system (CNS)-resident natural killer cells suppress Th17 responses and CNS autoimmune pathology.

Central nervous system (CNS)-resident natural killer cells suppress Th17 responses and CNS autoimmune pathology.
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DOI:
10.1084/jem.20092749
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发表时间:
2010-08-30
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Shi FD
Shi FD
中科院分区:
其他
文献类型:
--
作者:
Hao J;Liu R;Piao W;Zhou Q;Vollmer TL;Campagnolo DI;Xiang R;La Cava A;Van Kaer L;Shi FD

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先天免疫系统的自然杀伤(NK)细胞可以深刻影响适应性免疫反应的发展。在诸如中枢神经系统(CNS)的解剖位置中的炎症和自身免疫反应与在外周器官中发现的那些有很大不同。我们在多发性硬化症小鼠模型中发现,NK细胞富集导致疾病改善,而选择性阻断NK细胞归巢中枢神经系统导致疾病恶化。重要的是,NK细胞对CNS病理学的影响依赖于CNS驻留NK细胞的活性,而不是外周NK细胞。CNS驻留NK细胞的这种活性涉及与小胶质细胞的相互作用和对髓鞘反应性Th17细胞的抑制。我们的研究表明NK细胞对CNS炎症程度的器官特异性活性,为治疗干预提供了潜在的新靶点。
Natural killer (NK) cells of the innate immune system can profoundly impact the development of adaptive immune responses. Inflammatory and autoimmune responses in anatomical locations such as the central nervous system (CNS) differ substantially from those found in peripheral organs. We show in a mouse model of multiple sclerosis that NK cell enrichment results in disease amelioration, whereas selective blockade of NK cell homing to the CNS results in disease exacerbation. Importantly, the effects of NK cells on CNS pathology were dependent on the activity of CNS-resident, but not peripheral, NK cells. This activity of CNS-resident NK cells involved interactions with microglia and suppression of myelin-reactive Th17 cells. Our studies suggest an organ-specific activity of NK cells on the magnitude of CNS inflammation, providing potential new targets for therapeutic intervention.
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