MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration.
MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration.
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DOI：
10.1038/ncomms4633
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发表时间：
2014-04-16
影响因子：
16.6
通讯作者：
Sulzer, David
中科院分区：
文献类型：
--
作者：
Cebrian, Carolina;Zucca, Fabio A.;Mauri, Pierluigi;Steinbeck, Julius A.;Studer, Lorenz;Scherzer, Clemens R.;Kanter, Ellen;Budhu, Sadna;Mandelbaum, Jonathan;Vonsattel, Jean P.;Zecca, Luigi;Loike, John D.;Sulzer, David
据报道，啮齿动物神经元亚群表达主要组织相容性复合物 I 类 (MHC-I)，但在正常成人神经元中尚未报道这种表达。在这里，我们提供了来自死后样本的免疫标记、RNA 表达和质谱分析的证据，表明人类儿茶酚胺能黑质和蓝斑神经元表达 MHC-I，并且该分子在人类干细胞衍生的多巴胺 (DA) 神经元中是可诱导的。儿茶酚胺鼠培养神经元比其他神经元群体对 γ-干扰素诱导的 MHC-I 更敏感。神经元 MHC-I 也由神经黑色素或 α-突触核蛋白激活的小胶质细胞释放的因子或高胞质 DA 和/或氧化应激诱导。 DA 神经元内化外来卵清蛋白，并通过 MHC-I 展示源自该蛋白的抗原，在适当的细胞毒性 T 细胞存在时触发 DA 神经元死亡。因此，神经元 MHC-I 可以触发抗原反应，而儿茶酚胺神经元可能特别容易受到 T 细胞介导的细胞毒性攻击。
Subsets of rodent neurons are reported to express major histocompatibilty complex class I (MHC-I), but such expression has not been reported in normal adult human neurons. Here we provide evidence from immunolabel, RNA expression, and mass spectrometry analysis of postmortem samples that human catecholaminergic substantia nigra and locus coeruleus neurons express MHC-I, and that this molecule is inducible in human stem cell derived dopamine (DA) neurons. Catecholamine murine cultured neurons are more responsive to induction of MHC-I by gamma-interferon than other neuronal populations. Neuronal MHC-I is also induced by factors released from microglia activated by neuromelanin or alpha-synuclein, or high cytosolic DA and/or oxidative stress. DA neurons internalize foreign ovalbumin and display antigen derived from this protein by MHC-I, which triggers DA neuronal death in the presence of appropriate cytotoxic T-cells. Thus, neuronal MHC-I can trigger antigenic response, and catecholamine neurons may be particularly susceptible to T cell-mediated cytotoxic attack.
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影响因子：
3
作者：
Letellier, Mathieu;Willson, Melina L.;Lohof, Ann M.
通讯作者：
Lohof, Ann M.
影响因子：
6.7
作者：
Chevalier G;Suberbielle E;Monnet C;Duplan V;Martin-Blondel G;Farrugia F;Le Masson G;Liblau R;Gonzalez-Dunia D
通讯作者：
Gonzalez-Dunia D
影响因子：
64.8
作者：
Kriks, Sonja;Shim, Jae-Won;Piao, Jinghua;Ganat, Yosif M.;Wakeman, Dustin R.;Xie, Zhong;Carrillo-Reid, Luis;Auyeung, Gordon;Antonacci, Chris;Buch, Amanda;Yang, Lichuan;Beal, M. Flint;Surmeier, D. James;Kordower, Jeffrey H.;Tabar, Viviane;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
25
作者：
Glynn, Marian W.;Elmer, Bradford M.;Garay, Paula A.;Liu, Xiao-Bo;Needleman, Leigh A.;El-Sabeawy, Faten;McAllister, A. Kimberley
通讯作者：
McAllister, A. Kimberley
影响因子：
64.8
作者：
Harris, Tajie H.;Banigan, Edward J.;Christian, David A.;Konradt, Christoph;Wojno, Elia D. Tait;Norose, Kazumi;Wilson, Emma H.;John, Beena;Weninger, Wolfgang;Luster, Andrew D.;Liu, Andrea J.;Hunter, Christopher A.
通讯作者：
Hunter, Christopher A.