Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis.
Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis.
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DOI：
10.1016/j.jneuroim.2014.06.009
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发表时间：
2014-09-15
影响因子：
3.3
通讯作者：
Voskuhl, Rhonda R.
中科院分区：
文献类型：
--
作者：
Kim, Roy Y.;Hoffman, Alexandria S.;Itoh, Noriko;Ao, Yan;Spence, Rory;Sofroniew, Michael V.;Voskuhl, Rhonda R.
趋化因子（C-C基序）配体2（CCL 2）最初被鉴定为单核细胞趋化蛋白-1（MCP-1），在自身免疫性炎症期间将免疫细胞募集到中枢神经系统（CNS）。CCL 2可以由多种细胞类型表达，但在自身免疫性疾病的急性和慢性阶段，哪些细胞负责CCL 2功能尚不清楚。我们通过使用Cre-loxP基因缺失来确定CCL 2在实验性自身免疫性脑脊髓炎（EAE）中在体内星形胶质细胞中的作用。与野生型（WT）对照同窝出生的小鼠相比，具有来自星形胶质细胞的CCL 2的条件性基因缺失的小鼠在疾病晚期具有较不严重的EAE，而在发病时具有相似的发病率和疾病严重程度。与WT同窝仔相比，星形胶质细胞中缺乏CCL 2的EAE小鼠在脊髓的白色物质中具有较少的巨噬细胞和T细胞炎症，并且在白色和灰质中具有较少的星形胶质细胞和小胶质细胞的弥漫性活化以及较少的轴突损失和脱髓鞘。这些发现表明，星形胶质细胞中的CCL 2在慢性EAE期间持续募集免疫细胞和激活CNS中的胶质细胞中起重要作用，从而表明慢性神经炎性疾病的神经保护性治疗的新型细胞特异性靶点。
Chemokine (C-C motif) ligand 2 (CCL2), initially identified as monocyte chemoattractant protein-1 (MCP-1), recruits immune cells to the central nervous system (CNS) during autoimmune inflammation. CCL2 can be expressed by multiple cell types, but which cells are responsible for CCL2 function during acute and chronic phases of autoimmune disease is not known. We determined the role of CCL2 in astrocytes in vivo during experimental autoimmune encephalomyelitis (EAE) by using Cre-loxP gene deletion. Mice with a conditional gene deletion of CCL2 from astrocytes had less severe EAE late in disease while having a similar incidence and severity of disease at onset as compared to wild type (WT) control littermates. EAE mice devoid of CCL2 in astrocytes had less macrophage and T cell inflammation in the white matter of the spinal cord and less diffuse activation of astrocytes and microglia in both white and gray matter as well as less axonal loss and demyelination, compared to WT littermates. These findings demonstrate that CCL2 in astrocytes plays an important role in the continued recruitment of immune cells and activation of glial cells in the CNS during chronic EAE, thereby suggesting a novel cell specific target for neuroprotective treatments of chronic neuroinflammatory diseases.
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影响因子：
15.3
作者：
Brambilla, R;Bracchi-Ricard, V;Hu, WH;Frydel, B;Bramwell, A;Karmally, S;Green, EJ;Bethea, JR
通讯作者：
Bethea, JR
影响因子：
14.5
作者：
Bannerman, PG;Hahn, A;Pleasure, D
通讯作者：
Pleasure, D
影响因子：
3.1
作者：
Ge, Shujun;Murugesan, Nivetha;Pachter, Joel S.
通讯作者：
Pachter, Joel S.
影响因子：
11.2
作者：
Hauser, Stephen L.;Chan, Jonah R.;Oksenberg, Jorge R.
通讯作者：
Oksenberg, Jorge R.
DOI：
10.1523/jneurosci.1256-12.2012
发表时间：
2012-10-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hamby ME;Coppola G;Ao Y;Geschwind DH;Khakh BS;Sofroniew MV
通讯作者：
Sofroniew MV