M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination.
M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination.
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DOI：
10.1038/nn.3469
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发表时间：
2013-09
影响因子：
25
通讯作者：
Ffrench-Constant, Charles
中科院分区：
文献类型：
--
作者：
Miron, Veronique E.;Boyd, Amanda;Zhao, Jing-Wei;Yuen, Tracy J.;Ruckh, Julia M.;Shadrach, Jennifer L.;van Wijngaarden, Peter;Wagers, Amy J.;Williams, Anna;Franklin, Robin J. M.;Ffrench-Constant, Charles
进行性多发性硬化症缺乏治疗方法，这突出表明需要了解中枢神经系统脱髓鞘后髓鞘再生过程。这涉及由小胶质细胞/巨噬细胞组成的先天性免疫应答，其可以极化为不同的功能表型：促炎（M1）或抗炎/免疫调节（M2）。在这里，我们表明，从M1-M2-显性反应发生在小胶质细胞和外周衍生的巨噬细胞的髓鞘再生开始开关。少突胶质细胞的分化在体外增强与M2条件培养基，并在体内受损损伤内M2耗尽。M2密度增加，在病变的老年小鼠，其中髓鞘再生增强的联体耦合到一个年轻的动物，并在MS病变，通常显示髓鞘再生。阻断M2衍生的激活素A抑制小脑切片培养物中髓鞘再生过程中的少突胶质细胞分化。因此，我们的研究结果表明，M2极化是必要的有效髓鞘再生和确定激活素A作为一种新的治疗靶点中枢神经系统再生。
The lack of therapies for progressive multiple sclerosis highlights the need to understand the regenerative process of remyelination that can follow CNS demyelination. This involves an innate immune response consisting of microglia/macrophages, which can be polarized to distinct functional phenotypes: proinflammatory (M1) or anti-inflammatory/immunoregulatory (M2). Here we show that a switch from an M1- to M2-dominant response occurred within microglia and peripherally-derived macrophages as remyelination started. Oligodendrocyte differentiation was enhanced in vitro with M2 conditioned media, and impaired in vivo following intra-lesional M2 depletion. M2 densities were increased in lesions of aged mice in which remyelination was enhanced by parabiotic coupling to a younger animal, and in MS lesions that normally show remyelination. Blocking M2-derived activin-A inhibited oligodendrocyte differentiation during remyelination in cerebellar slice cultures. Our results therefore show that M2 polarization is essential for efficient remyelination and identify activin-A as a novel therapeutic target for CNS regeneration.
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影响因子：
25
作者：
Etxeberria A;Mangin JM;Aguirre A;Gallo V
通讯作者：
Gallo V
影响因子：
5.3
作者：
Liao, Bing;Zhao, Weihua;Beers, David R.;Henkel, Jenny S.;Appel, Stanley H.
通讯作者：
Appel, Stanley H.
DOI：
10.3390/molecules17010315
发表时间：
2011-12-30
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
He JT;Mang J;Mei CL;Yang L;Wang JQ;Xing Y;Yang H;Xu ZX
通讯作者：
Xu ZX
影响因子：
4.3
作者：
CASH, E;ZHANG, YP;ROTT, O
通讯作者：
ROTT, O
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG