Nitrated {alpha}-synuclein-induced alterations in microglial immunity are regulated by CD4+ T cell subsets.
Nitrated {alpha}-synuclein-induced alterations in microglial immunity are regulated by CD4+ T cell subsets.
复制标题
DOI：
10.4049/jimmunol.0803982
复制
发表时间：
2009-04-01
期刊：
影响因子：
--
通讯作者：
Gendelman HE
中科院分区：
文献类型：
--
作者：
Reynolds AD;Stone DK;Mosley RL;Gendelman HE
小胶质细胞炎症性神经调节活动影响帕金森病（PD）黑质纹状体变性的克里思。这些活动部分是由路易体内的错误折叠的硝化α-突触核蛋白（N-α-syn）诱导的，路易体是从垂死或死亡的多巴胺能神经元中释放出来的。这些病理生物学事件引发影响神经变性的先天性和适应性免疫应答。我们认为活化的小胶质细胞的神经生物学活性受到细胞-蛋白质和细胞-细胞接触的影响，因为小胶质细胞与N-α-syn和CD 4 + T细胞的相互作用实质性地改变了小胶质细胞蛋白质组。这导致细胞稳态功能的改变和疾病。CD 4 + CD 25+调节性T细胞（Treg）通过调节氧化还原活性酶、细胞迁移、吞噬作用和生物能蛋白表达及细胞功能来抑制N-α-syn小胶质细胞诱导的活性氧和核因子κ B活化。相比之下，CD 4 + CD 25 −效应T细胞加剧小胶质细胞炎症并诱导“推定的”神经毒性反应。这些数据支持适应性免疫在PD相关小胶质细胞炎症调节中的重要性。
Microglial inflammatory neuroregulatory activities affect the tempo of nigrostriatal degeneration during Parkinson's disease (PD). Such activities are induced, in part, by misfolded, nitrated alpha-synuclein (N-α-syn) within Lewy bodies released from dying or dead dopaminergic neurons. Such pathobiologic events initiate innate and adaptive immune responses affecting neurodegeneration. We posit that the neurobiological activities of activated microglia are affected by cell-protein and cell-cell contacts, in that microglial interactions with N-α-syn and CD4+ T cells substantively alter the microglial proteome. This leads to alterations in cell homeostatic functions and disease. CD4+CD25+ regulatory T cells (Treg) suppress N-α-syn microglial induced reactive oxygen species and nuclear factor kappa B activation by modulating redox-active enzymes, cell migration, phagocytosis, and bioenergetic protein expression and cell function. In contrast, CD4+CD25− effector T cells exacerbate microglial inflammation and induce “putative” neurotoxic responses. These data support the importance of adaptive immunity in the regulation of PD-associated microglial inflammation.
登录
查看更多内容
DOI：
10.1073/pnas.0400569101
发表时间：
2004-06-22
影响因子：
11.1
作者：
Benner, EJ;Mosley, RL;Gendelman, HE
通讯作者：
Gendelman, HE
影响因子：
6
作者：
Duda, JE;Giasson, BI;Trojanowski, JQ
通讯作者：
Trojanowski, JQ
影响因子：
15.9
作者：
Brochard, Vanessa;Combadiere, Behazine;Hunot, Stephane
通讯作者：
Hunot, Stephane
影响因子：
4
作者：
Bird, PI
通讯作者：
Bird, PI
影响因子：
3.7
作者：
Benner EJ;Banerjee R;Reynolds AD;Sherman S;Pisarev VM;Tsiperson V;Nemachek C;Ciborowski P;Przedborski S;Mosley RL;Gendelman HE
通讯作者：
Gendelman HE