IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype.
IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype.
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DOI：
10.1016/j.celrep.2012.02.014
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发表时间：
2012-04-19
期刊：
影响因子：
8.8
通讯作者：
Inoue K
中科院分区：
文献类型：
--
作者：
Masuda T;Tsuda M;Yoshinaga R;Tozaki-Saitoh H;Ozato K;Tamura T;Inoue K
小胶质细胞被神经系统中多种类型的损伤激活，并在神经元病理学中发挥重要作用。然而，小胶质细胞如何转化为反应性表型知之甚少。在这里，我们确定转录因子干扰素调节因子8（IRF 8）作为反应性小胶质细胞的关键调节因子。在脊髓内，IRF 8的表达通常较低;然而，在周围神经损伤（PNI）后，小胶质细胞中的表达显著上调，但在神经元或星形胶质细胞中则没有。IRF 8在培养的小胶质细胞中的过表达促进了与反应状态相关的基因的转录;相反，IRF 8缺乏阻止了PNI后脊髓中这些基因的表达。此外，IRF 8缺陷小鼠对神经性疼痛（PNI的常见后遗症）具有抗性，并且将IRF 8过表达的小胶质细胞脊髓转移到正常小鼠中产生疼痛。因此，IRF 8可能激活一个基因表达程序，将小胶质细胞转化为反应性表型。我们的研究结果提供了一个新观察到的小胶质细胞激活机制。
Microglia become activated by multiple types of damage in the nervous system and play essential roles in neuronal pathologies. However, how micro-glia transform into reactive phenotypes is poorly understood. Here, we identify the transcription factor interferon regulatory factor 8 (IRF8) as a critical regulator of reactive microglia. Within the spinal cord, IRF8 expression was normally low; however, the expression was markedly upregulated in microglia, but not in neurons or astrocytes, after peripheral nerve injury (PNI). IRF8 overexpression in cultured microglia promoted the transcription of genes associated with reactive states; conversely, IRF8 deficiency prevented these gene expressions in the spinal cord following PNI. Furthermore, IRF8-deficient mice were resistant to neuropathic pain, a common sequela of PNI, and transferring IRF8-over-expressing microglia spinally to normal mice produced pain. Therefore, IRF8 may activate a program of gene expression that transforms microglia into a reactive phenotype. Our findings provide a newly observed mechanism for microglial activation.
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影响因子：
3.1
作者：
BARBER, SA;FULTZ, MJ;VOGEL, SN
通讯作者：
VOGEL, SN
DOI：
10.1073/pnas.0610811104
发表时间：
2007-06-19
影响因子：
11.1
作者：
Clark, Anna K.;Yip, Ping K.;Malcangio, Marzia
通讯作者：
Malcangio, Marzia
影响因子：
25
作者：
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通讯作者：
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影响因子：
30.8
作者：
De Jager, Philip L.;Jia, Xiaoming;Wang, Joanne;de Bakker, Paul I. W.;Ottoboni, Linda;Aggarwal, Neelum T.;Piccio, Laura;Raychaudhuri, Soumya;Tran, Dong;Aubin, Cristin;Briskin, Rebeccah;Romano, Susan;Baranzini, Sergio E.;McCauley, Jacob L.;Pericak-Vance, Margaret A.;Haines, Jonathan L.;Gibson, Rachel A.;Naeglin, Yvonne;Uitdehaag, Bernard;Matthews, Paul M.;Kappos, Ludwig;Polman, Chris;McArdle, Wendy L.;Strachan, David P.;Evans, Denis;Cross, Anne H.;Daly, Mark J.;Compston, Alastair;Sawcer, Stephen J.;Weiner, Howard L.;Hauser, Stephen L.;Hafler, David A.;Oksenberg, Jorge R.
通讯作者：
Oksenberg, Jorge R.
影响因子：
64.8
作者：
Coull, JAM;Beggs, S;De Koninck, Y
通讯作者：
De Koninck, Y