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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Neuropilin-1 attenuates autoreactivity in experimental autoimmune encephalomyelitis
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Neuropilin-1 attenuates autoreactivity in experimental autoimmune encephalomyelitis

机译：Neuropilin-1减弱实验性自身免疫性脑脊髓炎的自身反应性

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摘要

Neuropilin-1 (Nrp1) is a cell surface molecule originally identified for its role in neuronal development. Recently, Nrpl has been implicated in several aspects of immune function including maintenance of the immune synapse and development of regulatory T (T_reg) cells. In this study, we provide evidence for a central role of Nrpl in the regulation of CD4 T-cell immune responses in experimental autoimmune encephalitis (EAE). EAE serves as an animal model for the central nervous system (CNS) inflammatory disorder multiple sclerosis (MS). EAE is mediated primarily by CD4~+ T cells that migrate to the CNS and mount an inflammatory attack against myelin components, resulting in CNS pathology. Using a tissue-specific deletion system, we observed that the lack of Nrpl on CD4~+ T cells results in increased EAE severity. These conditional knockout mice exhibit preferential T_h-17 lineage commitment and decreased T_reg-cell functionality. Conversely, CD4~+ T cells expressing Nrpl suppress effector T-cell proliferation and cytokine production both in vivo and in vitro independent of T_reg cells. Wrpl-mediated suppression can be inhibited by TGF-β blockade but not by IL-10 blockade. These results suggest that Nrpl is essential for proper maintenance of peripheral tolerance and its absence can result in unchecked autor-eactive responses, leading to diseases like EAE and potentially MS.
机译：Neuropilin-1（Nrp1）是最初鉴定为其在神经元发育中的作用的细胞表面分子。近来，Nrp1涉及免疫功能的多个方面，包括维持免疫突触和调节性T（T_reg）细胞的发育。在这项研究中，我们提供证据证明Nrpl在实验性自身免疫性脑炎（EAE）中调节CD4 T细胞免疫反应中的重要作用。 EAE可作为中枢神经系统（CNS）炎性疾病多发性硬化（MS）的动物模型。 EAE主要由CD4 + T细胞介导，该CD4 + T细胞迁移至CNS并对髓磷脂成分发炎性攻击，导致CNS病理。使用组织特异性缺失系统，我们观察到CD4〜+ T细胞上Nrpl的缺乏会导致EAE严重性增加。这些条件性基因敲除小鼠表现出优先的T_h-17血统承诺和减少的T_reg细胞功能。相反，表达Nrp1的CD4 + + T细胞在体内和体外均与T_reg细胞无关地抑制效应T细胞增殖和细胞因子的产生。 Wrp1介导的抑制作用可以被TGF-β阻滞抑制，而不能被IL-10阻滞抑制。这些结果表明，Nrpl对于适当维持周围耐受性至关重要，而Nrpl的缺乏会导致不受检查的主动反应，从而导致诸如EAE和潜在MS的疾病。

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    Benjamin D. Solomon; Cynthia Mueller; Wook-Jin Chae; Leah M. Alabanza; Margaret S. Bynoe;

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    Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853;

    Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853;

    Department of Immunobiology,Yale University School of Medicine, New Haven, CT 06520;

    Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853;

    Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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