HLA-DRα1-mMOG-35-55 treatment of experimental autoimmune encephalomyelitis reduces CNS inflammation, enhances M2 macrophage frequency, and promotes neuroprotection.
HLA-DRα1-mMOG-35-55 treatment of experimental autoimmune encephalomyelitis reduces CNS inflammation, enhances M2 macrophage frequency, and promotes neuroprotection.
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HLA-DRα1-MMOG-35-55治疗实验性自身免疫性脑脊髓炎可减少中枢神经系统炎症，增强M2巨噬细胞频率并促进神经保护作用。
DOI：
10.1186/s12974-015-0342-4
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发表时间：
2015-06-24
影响因子：
9.3
通讯作者：
Vandenbark AA
中科院分区：
文献类型：
--
作者：
Benedek G;Meza-Romero R;Jordan K;Keenlyside L;Offner H;Vandenbark AA
DRα1-mouse（m）MOG-35-55是我们实验室开发的一种新型构建体，作为双结构域II类构建体的一种更简单且潜在免疫原性更低的替代方案，先前已显示其靶向MIF/CD 74通路，并以与含亲本DR 2 β1构建体相似的方式逆转DR*1501-Tg小鼠中实验性自身免疫性脑脊髓炎（EAE）的临床和组织学体征。为了确定DRα1-mMOG-35-55是否可以治疗主要组织相容性复合体（MHC）错配小鼠中的EAE，并评价对中枢神经系统（CNS）炎症的治疗效果，用DRα1-mMOG-35-55处理C57 BL/6小鼠。此外，分析了接受DRα1-mMOG-35-55处理的EAE DR*1501-Tg小鼠脊髓中的基因表达谱。我们在此证明，DRα1-mMOG-35-55可通过减少CNS炎症有效治疗MHC不匹配C57 BL/6小鼠的EAE，可能部分通过增加脊髓中M2单核细胞的频率介导。DRα1-mMOG-35-55处理与溶剂对照EAE小鼠的脊髓组织微阵列分析显示，大量促炎基因（包括CD 74、NLRP 3和IL-1β）的表达降低，髓鞘修复（MBP）和神经再生（HUWE 1）相关基因的表达增加。这些发现表明，DRα1-mMOG-35-55构建体在EAE治疗期间跨越MHC不同屏障保留了治疗、抗炎和神经保护活性。本文的在线版本（doi：10.1186/s12974-015-0342-4）包含补充材料，可供授权用户使用。
DRα1-mouse(m)MOG-35-55, a novel construct developed in our laboratory as a simpler and potentially less immunogenic alternative to two-domain class II constructs, was shown previously to target the MIF/CD74 pathway and to reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in DR*1501-Tg mice in a manner similar to the parent DR2β1-containing construct. In order to determine whether DRα1-mMOG-35-55 could treat EAE in major histocompatibility complex (MHC)-mismatched mice and to evaluate the treatment effect on central nervous system (CNS) inflammation, C57BL/6 mice were treated with DRα1-mMOG-35-55. In addition, gene expression profile was analyzed in spinal cords of EAE DR*1501-Tg mice that were treated with DRα1-mMOG-35-55. We here demonstrate that DRα1-mMOG-35-55 could effectively treat EAE in MHC-mismatched C57BL/6 mice by reducing CNS inflammation, potentially mediated in part through an increased frequency of M2 monocytes in the spinal cord. Microarray analysis of spinal cord tissue from DRα1-mMOG-35-55-treated vs. vehicle control mice with EAE revealed decreased expression of a large number of pro-inflammatory genes including CD74, NLRP3, and IL-1β and increased expression of genes involved in myelin repair (MBP) and neuroregeneration (HUWE1). These findings indicate that the DRα1-mMOG-35-55 construct retains therapeutic, anti-inflammatory, and neuroprotective activities during treatment of EAE across MHC disparate barriers. The online version of this article (doi:10.1186/s12974-015-0342-4) contains supplementary material, which is available to authorized users.
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影响因子：
64.5
作者：
Cho Y;Sloutsky R;Naegle KM;Cavalli V
通讯作者：
Cavalli V
DOI：
10.4049/jimmunol.1303118
发表时间：
2014-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Meza-Romero R;Benedek G;Yu X;Mooney JL;Dahan R;Duvshani N;Bucala R;Offner H;Reiter Y;Burrows GG;Vandenbark AA
通讯作者：
Vandenbark AA
影响因子：
3.6
作者：
Benedek, Gil;Zhu, Wenbin;Offner, Halina
通讯作者：
Offner, Halina
DOI：
10.1523/jneurosci.2135-08.2008
发表时间：
2008-10-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kharebava G;Makonchuk D;Kalita KB;Zheng JJ;Hetman M
通讯作者：
Hetman M
影响因子：
25
作者：
Ajami, Bahareh;Bennett, Jami L.;Rossi, Fabio M. V.
通讯作者：
Rossi, Fabio M. V.